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研究生:蔡亞萍
研究生(外文):Ya-PingTsai
論文名稱:c-MYC誘導之細胞轉型與轉移乃藉由調控HSP60表現以促使β-catenin之活化
論文名稱(外文):Regulation of HSP60 by c-MYC contributes to c-MYC-induced transformation and metastasis through the activation of β-catenin
指導教授:吳國瑞
指導教授(外文):Kou-Juey Wu
學位類別:博士
校院名稱:國立陽明大學
系所名稱:生化暨分子生物研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:98
中文關鍵詞:熱休克蛋白60細胞轉型細胞轉移
外文關鍵詞:c-MYCHSP60β-catenintransformationmetastasis
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c-Myc 原致癌基因可轉譯為轉錄因子因此可參與細胞生長和增生以及與細胞癌化過程有關。熱休克蛋白60(HSP60) 在促使新合成蛋白質形成正確折疊結構當中扮演重要之角色。而在不同癌細胞之轉移機制當中,已知與β-catenin蛋白表現量之失調有關。本研究證實,c-MYC藉由結合熱休克蛋白60基因啓動子上E-box位置以誘導熱休克蛋白60之活化,並且熱休克蛋白60之過度表達可誘導細胞株轉移 (in vovo and in vitro)。本研究也發現,熱休克蛋白60藉由特定區域直接與β-catenin蛋白交互作用,進而增加β-catenin蛋白之表現並增強其轉錄活性。利用小片段干擾核醣核酸技術(short-interference RNA)抑制β-catenin蛋白可毀壞熱休克蛋白60過度表達所導致之癌細胞轉移。最後研究顯示,熱休克蛋白60及非細胞膜β-catenin蛋白共同表現於頭頸癌(head and neck squamous cell carcinoma)病人檢體當中,因此可作為癌症病患之癒後不良的指標。綜合以上結果,本研究證實c-MYC誘導之細胞轉型與轉移乃藉由調控HSP60表現以促使β-catenin之活化。
The c-MYC proto-oncogene encodes a ubiquitous transcription factor involved in the control of cell growth and proliferation, and implicated in tumorigenesis. Heat shock protein 60 (HSP60) plays an essential role in assisting many newly synthesized proteins to reach their native forms. Deregulation of β-catenin was shown to be related to different types of cancer with metastasis. Here, the results show that c-MYC directly activates HSP60 transcription, and the activation is mediated by an E-box (CACGTG) site located in the proximal promoter of the HSP60 gene. Overexpression of HSP60 induces metastatic phenotypes in vitro and in vivo. HSP60 increases β-catenin protein levels and enhances its transcriptional activity through interaction with β-catenin using a specific HSP60 domain. siRNA (short-interference RNA) mediated repression of β-catenin abolishes metastatic activity caused by HSP60 overexpression. Co-expression of HSP60 and non-membranous β-catenin predicts a worse prognosis of metastatic head and neck cancer patients. These results indicate that c-MYC may promote transformation and metastasis by induction of HSP60 and subsequent activation of β-catenin.
Abbreviation..........................................1
Abstract (English)....................................3
Abstract (Chinese)....................................4
Introduction
Ⅰ. c-MYC............................................5
Ⅱ. HSP60............................................8
Ⅲ. β-catenin.......................................11
Materials and Methods................................14
Cell lines and reagents.............................14
Plasmids............................................15
RNA purification and cDNA synthesis.................17
Quantitative real-time PCR..........................17
Northern Blot Analysis..............................17
Luciferase assays...................................18
Chromatin immunoprecipitation (ChIP) assays.........18
Soft agar clonogenicity assay.......................19
Western blot analysis...............................19
Co-immunoprecipitation assays.......................20
In vitro dephosphorylation assays...................20
GST pull down assay.................................21
Immunofluorescence..................................22
In vitro migration/invasion assays..................23
In vivo tail vein metastasis assays.................23
Study population and sample collection..............24
Tissue microarray construction......................24
Immunohistochemstry (IHC) and scoring...............25
Statistical analysis................................25
Results..............................................27
Correlation between c-MYC and HSP60 expression......27
Direction regulation of HSP60 by c-MYC..............28
Overexpression of HSP60 induces transformation......29
Overexpression of HSP60 induces metastasis..........30
Interaction between HSP60 and β-catenin............31
Activation of β-catenin pathway by HSP60
overexpression......................................32
The critical role of β-catenin in vitro and in
vivo metastasis activity............................33
Induction of β-catenin levels by HSP60 does not
require proteosomal activity........................34
Positive autoregulation of c-MYC activity by HSP60
overexpression......................................35
The role of β-catenin in c-MYC-induced transformation
and metastasis......................................36
Co-expression of HSP60 and β-catenin predicts a poor
prognosis in HNSCC patients.........................37
Discussion...........................................38
Figures..............................................41
Figure 1.Activation of HSP60 mRNA and protein
expression by c-MYC in different cell
lines.....................................41
Figure 2.Direct activation of HSP60 expression by
c-MYC.....................................43
Figure 3.HSP60 overexpression increased the
transformation activity of Rat1a cell line
in vitro..................................45
Figure 4.HSP60 overexpression increases migration,
invasion and metastasis of FADU cell line.47
Figure 5.siRNA mediated repression of endogenous
HSP60 in RatMyc cells decreased the
migration and invasion activity...........49
Figure 6.Interaction between β-catenin and HSP60
in FADUHSP60 cells as well as in 293T cells,
overexpressing both proteins, and domain
mapping in HSP60 and β-catenin...........50
Figure 7.Immunofluorescence co-localization of HSP60
and β-catenin, and mapping of the
interaction domain in β-catenin and HSP60
by GST pull down assay....................52
Figure 8.HSP60 overexpression increases the protein
levels of β-catenin and 14-3-3zeta, but
not other control proteins................54
Figure 9.Activation of β-catenin and its downstream
targets, enhancement of its transcriptional
activity and the critical role of HSP60 in
β-catenin activation.....................56
Figure 10.β-catenin is critical for the migration
and invasion activity induced by HSP60
overexpression............................57
Figure 11.β-catenin is critical for the migration
and invasion activity.....................59
Figure 12.The ability of HSP60 to increase β-catenin
protein levels does not go through the
proteasome pathway.......................60
Figure 13.HSP60 increases transcription activity of
ubiquitinated β-catenin.................62
Figure 14.Positive autoregulation of c-MYC activity
by HSP60 overexpression..................63
Figure 15.β-catenin is not critical for the
migration and invasion activity induced
by c-MYC overexpression...................64
Figure 16.Co-expression of HSP60 and non-membranous
β-catenin predicted a worse progno is of
metastatic HNSCC patients.................66
Figure 17.Overexpression of WNT-1 and its association
with HSP60 expression in primary and
metastatic HNSCC tumors...................68
Figure 18.Schematic diagram of the proposed signaling
mechanism that HSP60, c-MYC target gene,
contributes to c-MYC-induced metastasis
through the activation of β-catenin......69
Tables...............................................70
Table 1. List of proteins tested by and
characteristics of the corresponding
antibodies.................................70
Table 2. Sequence of the oligonuleotides for
constructions..............................72
Table 3. Plasmid construction.......................74
Table 4. Sequence of the oligonucleorides for siRNA
experiment, real-time PCR and ChIP assay...75
Table 5. Characteristics and univariate analysis of
overall survival in 58 metastatic HNSCC
patients...................................76
Table 6. The association between HSP60, WNT-1
everexpressionand non-membranous expression
of β-catenin in primary and metastatic
samples of 58 HNSCC cases..................78
Table 7. Multivariate analysis of overall survival..78
Table 8. Correlation between HSP60 / nuclear
β-catenin expression in HNSCC metastatic
tumor and clinical variables...............79
Reference............................................80
Aberle, H., Bauer, A., Stappert, J., Kispert, A., and Kemler, R. (1997). beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 16, 3797-3804.
Adhikary, S., and Eilers, M. (2005). Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 6, 635-645.
Arnold, I., and Watt, F.M. (2001). c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr Biol 11, 558-568.
Ayer, D.E., and Eisenman, R.N. (1993). A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. Genes Dev 7, 2110-2119.
Baldus, S.E., Monig, S.P., Huxel, S., Landsberg, S., Hanisch, F.G., Engelmann, K., Schneider, P.M., Thiele, J., Holscher, A.H., and Dienes, H.P. (2004). MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res 10, 2790-2796.
Barazi, H.O., Zhou, L., Templeton, N.S., Krutzsch, H.C., and Roberts, D.D. (2002). Identification of heat shock protein 60 as a molecular mediator of alpha 3 beta 1 integrin activation. Cancer Res 62, 1541-1548.
Baudino, T.A., McKay, C., Pendeville-Samain, H., Nilsson, J.A., Maclean, K.H., White, E.L., Davis, A.C., Ihle, J.N., and Cleveland, J.L. (2002). c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. Genes Dev 16, 2530-2543.
Blackwell, T.K., Huang, J., Ma, A., Kretzner, L., Alt, F.W., Eisenman, R.N., and Weintraub, H. (1993). Binding of myc proteins to canonical and noncanonical DNA sequences. Mol Cell Biol 13, 5216-5224.
Blackwell, T.K., Kretzner, L., Blackwood, E.M., Eisenman, R.N., and Weintraub, H. (1990). Sequence-specific DNA binding by the c-Myc protein. Science 250, 1149-1151.
Blackwood, E.M., and Eisenman, R.N. (1991). Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 251, 1211-1217.
Blackwood, E.M., Luscher, B., and Eisenman, R.N. (1992). Myc and Max associate in vivo. Genes Dev 6, 71-80.
Brabletz, T., Jung, A., Dag, S., Hlubek, F., and Kirchner, T. (1999). beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol 155, 1033-1038.
Brembeck, F.H., Rosario, M., and Birchmeier, W. (2006). Balancing cell adhesion and Wnt signaling, the key role of beta-catenin. Curr Opin Genet Dev 16, 51-59.
Bukau, B., and Horwich, A.L. (1998). The Hsp70 and Hsp60 chaperone machines. Cell 92, 351-366.
Cadigan, K.M., and Liu, Y.I. (2006). Wnt signaling: complexity at the surface. J Cell Sci 119, 395-402.
Cappello, F., Bellafiore, M., Palma, A., David, S., Marciano, V., Bartolotta, T., Sciume, C., Modica, G., Farina, F., Zummo, G., et al. (2003). 60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis. Eur J Histochem 47, 105-110.
Cappello, F., Bellafiore, M., Palma, A., Marciano, V., Martorana, G., Belfiore, P., Martorana, A., Farina, F., Zummo, G., and Bucchieri, F. (2002). Expression of 60-kD heat shock protein increases during carcinogenesis in the uterine exocervix. Pathobiology 70, 83-88.
Cappello, F., David, S., Rappa, F., Bucchieri, F., Marasa, L., Bartolotta, T.E., Farina, F., and Zummo, G. (2005). The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer 5, 139.
Chatellier, J., Hill, F., Lund, P.A., and Fersht, A.R. (1998). In vivo activities of GroEL minichaperones. Proc Natl Acad Sci U S A 95, 9861-9866.
Chen, G., Shukeir, N., Potti, A., Sircar, K., Aprikian, A., Goltzman, D., and Rabbani, S.A. (2004). Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications. Cancer 101, 1345-1356.
Chen, Y.C., Hsu, H.S., Chen, Y.W., Tsai, T.H., How, C.K., Wang, C.Y., Hung, S.C., Chang, Y.L., Tsai, M.L., Lee, Y.Y., et al. (2008). Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS ONE 3, e2637.
Cheng, M.Y., Hartl, F.U., and Horwich, A.L. (1990). The mitochondrial chaperonin hsp60 is required for its own assembly. Nature 348, 455-458.
Cheng, M.Y., Hartl, F.U., Martin, J., Pollock, R.A., Kalousek, F., Neupert, W., Hallberg, E.M., Hallberg, R.L., and Horwich, A.L. (1989). Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 337, 620-625.
Chiang, Y.C., Teng, S.C., Su, Y.N., Hsieh, F.J., and Wu, K.J. (2003). c-Myc directly regulates the transcription of the NBS1 gene involved in DNA double-strand break repair. J Biol Chem 278, 19286-19291.
Cornford, P.A., Dodson, A.R., Parsons, K.F., Desmond, A.D., Woolfenden, A., Fordham, M., Neoptolemos, J.P., Ke, Y., and Foster, C.S. (2000). Heat shock protein expression independently predicts clinical outcome in prostate cancer. Cancer Res 60, 7099-7105.
Cowling, V.H., and Cole, M.D. (2006). Mechanism of transcriptional activation by the Myc oncoproteins. Semin Cancer Biol 16, 242-252.
Crawford, H.C., Fingleton, B.M., Rudolph-Owen, L.A., Goss, K.J., Rubinfeld, B., Polakis, P., and Matrisian, L.M. (1999). The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene 18, 2883-2891.
Crockett, D.K., Lin, Z., Elenitoba-Johnson, K.S., and Lim, M.S. (2004). Identification of NPM-ALK interacting proteins by tandem mass spectrometry. Oncogene 23, 2617-2629.
Dalla-Favera, R., Bregni, M., Erikson, J., Patterson, D., Gallo, R.C., and Croce, C.M. (1982a). Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A 79, 7824-7827.
Dalla-Favera, R., Gelmann, E.P., Martinotti, S., Franchini, G., Papas, T.S., Gallo, R.C., and Wong-Staal, F. (1982b). Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A 79, 6497-6501.
de Alboran, I.M., O'Hagan, R.C., Gartner, F., Malynn, B., Davidson, L., Rickert, R., Rajewsky, K., DePinho, R.A., and Alt, F.W. (2001). Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14, 45-55.
De Benedetti, A., and Graff, J.R. (2004). eIF-4E expression and its role in malignancies and metastases. Oncogene 23, 3189-3199.
Dominguez-Sola, D., Ying, C.Y., Grandori, C., Ruggiero, L., Chen, B., Li, M., Galloway, D.A., Gu, W., Gautier, J., and Dalla-Favera, R. (2007). Non-transcriptional control of DNA replication by c-Myc. Nature 448, 445-451.
Drees, F., Pokutta, S., Yamada, S., Nelson, W.J., and Weis, W.I. (2005). Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly. Cell 123, 903-915.
Fang, D., Hawke, D., Zheng, Y., Xia, Y., Meisenhelder, J., Nika, H., Mills, G.B., Kobayashi, R., Hunter, T., and Lu, Z. (2007). Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. J Biol Chem 282, 11221-11229.
Felsher, D.W., and Bishop, J.M. (1999). Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Proc Natl Acad Sci U S A 96, 3940-3944.
Fernandez, P.C., Frank, S.R., Wang, L., Schroeder, M., Liu, S., Greene, J., Cocito, A., and Amati, B. (2003). Genomic targets of the human c-Myc protein. Genes Dev 17, 1115-1129.
Gavert, N., and Ben-Ze'ev, A. (2007). beta-Catenin signaling in biological control and cancer. J Cell Biochem 102, 820-828.
Ghosh, J.C., Dohi, T., Kang, B.H., and Altieri, D.C. (2008). Hsp60 regulation of tumor cell apoptosis. J Biol Chem 283, 5188-5194.
Gu, W., Cechova, K., Tassi, V., and Dalla-Favera, R. (1993). Opposite regulation of gene transcription and cell proliferation by c-Myc and Max. Proc Natl Acad Sci U S A 90, 2935-2939.
Gupta, S., and Knowlton, A.A. (2002). Cytosolic heat shock protein 60, hypoxia, and apoptosis. Circulation 106, 2727-2733.
Habich, C., and Burkart, V. (2007). Heat shock protein 60: regulatory role on innate immune cells. Cell Mol Life Sci 64, 742-751.
He, T.C., Sparks, A.B., Rago, C., Hermeking, H., Zawel, L., da Costa, L.T., Morin, P.J., Vogelstein, B., and Kinzler, K.W. (1998). Identification of c-MYC as a target of the APC pathway. Science 281, 1509-1512.
Herold, S., Wanzel, M., Beuger, V., Frohme, C., Beul, D., Hillukkala, T., Syvaoja, J., Saluz, H.P., Haenel, F., and Eilers, M. (2002). Negative regulation of the mammalian UV response by Myc through association with Miz-1. Mol Cell 10, 509-521.
Hiendlmeyer, E., Regus, S., Wassermann, S., Hlubek, F., Haynl, A., Dimmler, A., Koch, C., Knoll, C., van Beest, M., Reuning, U., et al. (2004). Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors. Cancer Res 64, 1209-1214.
Hlubek, F., Jung, A., Kotzor, N., Kirchner, T., and Brabletz, T. (2001). Expression of the invasion factor laminin gamma2 in colorectal carcinomas is regulated by beta-catenin. Cancer Res 61, 8089-8093.
Hlubek, F., Spaderna, S., Jung, A., Kirchner, T., and Brabletz, T. (2004). Beta-catenin activates a coordinated expression of the proinvasive factors laminin-5 gamma2 chain and MT1-MMP in colorectal carcinomas. Int J Cancer 108, 321-326.
Ikawa, S., and Weinberg, R.A. (1992). An interaction between p21ras and heat shock protein hsp60, a chaperonin. Proc Natl Acad Sci U S A 89, 2012-2016.
Imai, T., Horiuchi, A., Shiozawa, T., Osada, R., Kikuchi, N., Ohira, S., Oka, K., and Konishi, I. (2004). Elevated expression of E-cadherin and alpha-, beta-, and gamma-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas. Hum Pathol 35, 1469-1476.
Iritani, B.M., and Eisenman, R.N. (1999). c-Myc enhances protein synthesis and cell size during B lymphocyte development. Proc Natl Acad Sci U S A 96, 13180-13185.
Ishida, K., Ito, S., Wada, N., Deguchi, H., Hata, T., Hosoda, M., and Nohno, T. (2007). Nuclear localization of beta-catenin involved in precancerous change in oral leukoplakia. Mol Cancer 6, 62.
Isidoro, A., Casado, E., Redondo, A., Acebo, P., Espinosa, E., Alonso, A.M., Cejas, P., Hardisson, D., Fresno Vara, J.A., Belda-Iniesta, C., et al. (2005). Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis. Carcinogenesis 26, 2095-2104.
Iwai, S., Katagiri, W., Kong, C., Amekawa, S., Nakazawa, M., and Yura, Y. (2005). Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma. J Cancer Res Clin Oncol 131, 773-782.
Iwaya, K., Ogawa, H., Kuroda, M., Izumi, M., Ishida, T., and Mukai, K. (2003). Cytoplasmic and/or nuclear staining of beta-catenin is associated with lung metastasis. Clin Exp Metastasis 20, 525-529.
Johnston, L.A., Prober, D.A., Edgar, B.A., Eisenman, R.N., and Gallant, P. (1999). Drosophila myc regulates cellular growth during development. Cell 98, 779-790.
Kaidi, A., Williams, A.C., and Paraskeva, C. (2007). Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia. Nat Cell Biol 9, 210-217.
Kempkes, B., Spitkovsky, D., Jansen-Durr, P., Ellwart, J.W., Kremmer, E., Delecluse, H.J., Rottenberger, C., Bornkamm, G.W., and Hammerschmidt, W. (1995). B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2. EMBO J 14, 88-96.
Khan, I.U., Wallin, R., Gupta, R.S., and Kammer, G.M. (1998). Protein kinase A-catalyzed phosphorylation of heat shock protein 60 chaperone regulates its attachment to histone 2B in the T lymphocyte plasma membrane. Proc Natl Acad Sci U S A 95, 10425-10430.
Kim, K., Lu, Z., and Hay, E.D. (2002). Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT. Cell Biol Int 26, 463-476.
Kirchhoff, S.R., Gupta, S., and Knowlton, A.A. (2002). Cytosolic heat shock protein 60, apoptosis, and myocardial injury. Circulation 105, 2899-2904.
Koll, H., Guiard, B., Rassow, J., Ostermann, J., Horwich, A.L., Neupert, W., and Hartl, F.U. (1992). Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane space. Cell 68, 1163-1175.
Li, F.Q., Mofunanya, A., Harris, K., and Takemaru, K. (2008). Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity. J Cell Biol 181, 1141-1154.
Lin, K.M., Lin, B., Lian, I.Y., Mestril, R., Scheffler, I.E., and Dillmann, W.H. (2001). Combined and individual mitochondrial HSP60 and HSP10 expression in cardiac myocytes protects mitochondrial function and prevents apoptotic cell deaths induced by simulated ischemia-reoxygenation. Circulation 103, 1787-1792.
Littlewood, T.D., Hancock, D.C., Danielian, P.S., Parker, M.G., and Evan, G.I. (1995). A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res 23, 1686-1690.
Lu, Z., and Hunter, T. (2004). Wnt-independent beta-catenin transactivation in tumor development. Cell Cycle 3, 571-573.
Mateyak, M.K., Obaya, A.J., Adachi, S., and Sedivy, J.M. (1997). Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination. Cell Growth Differ 8, 1039-1048.
Mateyak, M.K., Obaya, A.J., and Sedivy, J.M. (1999). c-Myc regulates cyclin D-Cdk4 and -Cdk6 activity but affects cell cycle progression at multiple independent points. Mol Cell Biol 19, 4672-4683.
Medici, D., Hay, E.D., and Olsen, B.R. (2008). Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell 19, 4875-4887.
Meyer, N., and Penn, L.Z. (2008). Reflecting on 25 years with MYC. Nat Rev Cancer 8, 976-990.
Morin, P.J., Sparks, A.B., Korinek, V., Barker, N., Clevers, H., Vogelstein, B., and Kinzler, K.W. (1997). Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275, 1787-1790.
Morrison, J.A., Klingelhutz, A.J., and Raab-Traub, N. (2003). Epstein-Barr virus latent membrane protein 2A activates beta-catenin signaling in epithelial cells. J Virol 77, 12276-12284.
Muller, T., Bain, G., Wang, X., and Papkoff, J. (2002). Regulation of epithelial cell migration and tumor formation by beta-catenin signaling. Exp Cell Res 280, 119-133.
Nielsen, K.L., and Cowan, N.J. (1998). A single ring is sufficient for productive chaperonin-mediated folding in vivo. Mol Cell 2, 93-99.
O'Connell, B.C., Cheung, A.F., Simkevich, C.P., Tam, W., Ren, X., Mateyak, M.K., and Sedivy, J.M. (2003). A large scale genetic analysis of c-Myc-regulated gene expression patterns. J Biol Chem 278, 12563-12573.
Ostermann, J., Horwich, A.L., Neupert, W., and Hartl, F.U. (1989). Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysis. Nature 341, 125-130.
Pelengaris, S., Khan, M., and Evan, G.I. (2002). Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 109, 321-334.
Persson, H., and Leder, P. (1984). Nuclear localization and DNA binding properties of a protein expressed by human c-myc oncogene. Science 225, 718-721.
Pignatelli, D., Ferreira, J., Soares, P., Costa, M.J., and Magalhaes, M.C. (2003). Immunohistochemical study of heat shock proteins 27, 60 and 70 in the normal human adrenal and in adrenal tumors with suppressed ACTH production. Microsc Res Tech 61, 315-323.
Piselli, P., Vendetti, S., Vismara, D., Cicconi, R., Poccia, F., Colizzi, V., and Delpino, A. (2000). Different expression of CD44, ICAM-1, and HSP60 on primary tumor and metastases of a human pancreatic carcinoma growing in scid mice. Anticancer Res 20, 825-831.
Samali, A., Cai, J., Zhivotovsky, B., Jones, D.P., and Orrenius, S. (1999). Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells. EMBO J 18, 2040-2048.
Schneider, J., Jimenez, E., Marenbach, K., Romero, H., Marx, D., and Meden, H. (1999). Immunohistochemical detection of HSP60-expression in human ovarian cancer. Correlation with survival in a series of 247 patients. Anticancer Res 19, 2141-2146.
Shamaei-Tousi, A., Halcox, J.P., and Henderson, B. (2007). Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease. Cardiovasc Res 74, 19-28.
Shan, Y.X., Liu, T.J., Su, H.F., Samsamshariat, A., Mestril, R., and Wang, P.H. (2003). Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signaling induced by doxorubicin in cardiac muscle cells. J Mol Cell Cardiol 35, 1135-1143.
Shekhar, M.P., Gerard, B., Pauley, R.J., Williams, B.O., and Tait, L. (2008). Rad6B is a positive regulator of beta-catenin stabilization. Cancer Res 68, 1741-1750.
Shin, B.K., Wang, H., Yim, A.M., Le Naour, F., Brichory, F., Jang, J.H., Zhao, R., Puravs, E., Tra, J., Michael, C.W., et al. (2003). Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J Biol Chem 278, 7607-7616.
Smiley, J.K., Brown, W.C., and Campbell, J.L. (1992). The 66 kDa component of yeast SFI, stimulatory factor I, is hsp60. Nucleic Acids Res 20, 4913-4918.
Soltys, B.J., Falah, M., and Gupta, R.S. (1996). Identification of endoplasmic reticulum in the primitive eukaryote Giardia lamblia using cryoelectron microscopy and antibody to Bip. J Cell Sci 109 ( Pt 7), 1909-1917.
Soltys, B.J., and Gupta, R.S. (1996). Immunoelectron microscopic localization of the 60-kDa heat shock chaperonin protein (Hsp60) in mammalian cells. Exp Cell Res 222, 16-27.
Soltys, B.J., and Gupta, R.S. (1997). Cell surface localization of the 60 kDa heat shock chaperonin protein (hsp60) in mammalian cells. Cell Biol Int 21, 315-320.
Soltys, B.J., and Gupta, R.S. (1999). Mitochondrial-matrix proteins at unexpected locations: are they exported? Trends Biochem Sci 24, 174-177.
Stadeli, R., Hoffmans, R., and Basler, K. (2006). Transcription under the control of nuclear Arm/beta-catenin. Curr Biol 16, R378-385.
Sun, C., Yamato, T., Kondo, E., Furukawa, T., Ikeda, H., and Horii, A. (2005). Infrequent mutation of APC, AXIN1, and GSK3B in human pituitary adenomas with abnormal accumulation of CTNNB1. J Neurooncol 73, 131-134.
Takahashi, M., Tsunoda, T., Seiki, M., Nakamura, Y., and Furukawa, Y. (2002). Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene 21, 5861-5867.
Teng, S.C., Chen, Y.Y., Su, Y.N., Chou, P.C., Chiang, Y.C., Tseng, S.F., and Wu, K.J. (2004). Direct activation of HSP90A transcription by c-Myc contributes to c-Myc-induced transformation. J Biol Chem 279, 14649-14655.
Tetsu, O., and McCormick, F. (1999). Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398, 422-426.
Tian, Q., Feetham, M.C., Tao, W.A., He, X.C., Li, L., Aebersold, R., and Hood, L. (2004). Proteomic analysis identifies that 14-3-3zeta interacts with beta-catenin and facilitates its activation by Akt. Proc Natl Acad Sci U S A 101, 15370-15375.
Trumpp, A., Refaeli, Y., Oskarsson, T., Gasser, S., Murphy, M., Martin, G.R., and Bishop, J.M. (2001). c-Myc regulates mammalian body size by controlling cell number but not cell size. Nature 414, 768-773.
Urushibara, M., Kageyama, Y., Akashi, T., Otsuka, Y., Takizawa, T., Koike, M., and Kihara, K. (2007). HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer. Jpn J Clin Oncol 37, 56-61.
van der Horst, A., de Vries-Smits, A.M., Brenkman, A.B., van Triest, M.H., van den Broek, N., Colland, F., Maurice, M.M., and Burgering, B.M. (2006). FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol 8, 1064-1073.
Venuprasad, K., Huang, H., Harada, Y., Elly, C., Subramaniam, M., Spelsberg, T., Su, J., and Liu, Y.C. (2008). The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG1. Nat Immunol 9, 245-253.
Verdegaal, M.E., Zegveld, S.T., and van Furth, R. (1996). Heat shock protein 65 induces CD62e, CD106, and CD54 on cultured human endothelial cells and increases their adhesiveness for monocytes and granulocytes. J Immunol 157, 369-376.
Vervoorts, J., Luscher-Firzlaff, J.M., Rottmann, S., Lilischkis, R., Walsemann, G., Dohmann, K., Austen, M., and Luscher, B. (2003). Stimulation of c-MYC transcriptional activity and acetylation by recruitment of the cofactor CBP. EMBO Rep 4, 484-490.
Wadhwa, R., Takano, S., Kaur, K., Aida, S., Yaguchi, T., Kaul, Z., Hirano, T., Taira, K., and Kaul, S.C. (2005). Identification and characterization of molecular interactions between mortalin/mtHsp70 and HSP60. Biochem J 391, 185-190.
Wang, H., Mannava, S., Grachtchouk, V., Zhuang, D., Soengas, M.S., Gudkov, A.V., Prochownik, E.V., and Nikiforov, M.A. (2007). c-Myc depletion inhibits proliferation of human tumor cells at various stages of the cell cycle. Oncogene.
Wanzel, M., Herold, S., and Eilers, M. (2003). Transcriptional repression by Myc. Trends Cell Biol 13, 146-150.
Wilson, A., Murphy, M.J., Oskarsson, T., Kaloulis, K., Bettess, M.D., Oser, G.M., Pasche, A.C., Knabenhans, C., Macdonald, H.R., and Trumpp, A. (2004). c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev 18, 2747-2763.
Wu, C.H., van Riggelen, J., Yetil, A., Fan, A.C., Bachireddy, P., and Felsher, D.W. (2007). Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc Natl Acad Sci U S A 104, 13028-13033.
Wu, K.J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., and Dalla-Favera, R. (1999a). Direct activation of TERT transcription by c-MYC. Nat Genet 21, 220-224.
Wu, K.J., Polack, A., and Dalla-Favera, R. (1999b). Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science 283, 676-679.
Xu, W., and Kimelman, D. (2007). Mechanistic insights from structural studies of beta-catenin and its binding partners. J Cell Sci 120, 3337-3344.
Yang, M.H., Chang, S.Y., Chiou, S.H., Liu, C.J., Chi, C.W., Chen, P.M., Teng, S.C., and Wu, K.J. (2007). Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer. Oncogene 26, 1459-1467.
Yang, M.H., Wu, M.Z., Chiou, S.H., Chen, P.M., Chang, S.Y., Liu, C.J., Teng, S.C., and Wu, K.J. (2008). Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol.
Yi, F., Jaffe, R., and Prochownik, E.V. (2003). The CCL6 chemokine is differentially regulated by c-Myc and L-Myc, and promotes tumorigenesis and metastasis. Cancer Res 63, 2923-2932.
Young, J.C., Agashe, V.R., Siegers, K., and Hartl, F.U. (2004). Pathways of chaperone-mediated protein folding in the cytosol. Nat Rev Mol Cell Biol 5, 781-791.
Zhang, W.M., Lo Muzio, L., Rubini, C., and Yan, G. (2005a). Effect of WNT-1 on beta-catenin expression and its relation to Ki-67 and tumor differentiation in oral squamous cell carcinoma. Oncol Rep 13, 1095-1099.
Zhang, X.Y., DeSalle, L.M., Patel, J.H., Capobianco, A.J., Yu, D., Thomas-Tikhonenko, A., and McMahon, S.B. (2005b). Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein. Proc Natl Acad Sci U S A 102, 13968-13973.
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