臺灣博碩士論文加值系統

本篇論文研究目的為評估nm23-H1蛋白於子宮頸正常、癌前和癌組織之表現情形，以及其在子宮頸癌化過程中所扮演的角色。總共蒐集86個子宮頸病理樣本，包括30個子宮頸鱗狀上皮癌 (squamous cell carcinoma; SCC)、3個腺癌 (adenocarcinoma)、1個明亮細胞癌(clear cell carcinoma)、19個高度和13個低度子宮頸鱗狀上皮內病變(high-grade and low-grade squamous intraepithelial lesions; HSILs and LSILs) 暨20個正常子宮頸檢体。這些檢体用免疫組織化學法，並以streptavidin-biotin peroxidase方式行免疫染色。更進一步，對其中30個子宮頸鱗狀上皮癌病例，探討nm23-H1蛋白表現和癌症病人臨床病理特徵之關係。此外，並評估這些病人之累計復發危險性(cumulative recurrence hazard)。
以卡方試驗 (Chi-square test)、Fisher’s exact試驗及卡方趨勢檢定(Chi-square test for trend) 比較nm23-H1蛋白在子宮頸正常、低度和高度鱗狀上皮內病變及癌組織之表現情形。以Fisher’s exact試驗評估nm23-H1蛋白表現和癌症病人臨床病理特徵之關係。這些臨床病理特徵包括年齡 (大於等於或小於50歲)、分化層級 (分化好、中等或不好)、基質侵犯深度 (大於等於或小於基質1/2侵犯深度) 及癌症轉移情形 (淋巴、子宮旁或陰道轉移)。再將癌症病人依nm23-H1蛋白表現高低分成兩組，並畫出累計復發危險性之Kaplan-Meier曲線，且以long-rank試驗比較nm23-H1蛋白表現高和低兩組隨著時間其復發分佈 (recurrence distributions) 之差異。
結果發現，有統計差異之nm23-H1蛋白表現，出現於低度和高度子宮頸鱗狀上皮內病變檢体之間 (P = 0.016) 以及低度子宮頸鱗狀上皮內病變和子宮頸鱗狀上皮癌檢体之間 (P = 0.002)，然而nm23-H1蛋白之表現於高度子宮頸鱗狀上皮內病變和子宮頸鱗狀上皮癌檢体之間以及正常子宮頸和低度子宮頸鱗狀上皮內病變檢体之間則未有統計上的差異。更進一步發現，子宮頸病變愈厲害，nm23-H1蛋白有表現愈高的趨勢 (P < 0.05)。而於眾多臨床病理特徵當中，只有大於等於基質1/2侵犯深度和nm23-H1蛋白之高度表現呈現統計學上有意義的關連 ( P = 0.003)。甚且，nm23-H1蛋白高度表現之組別，有較高之累計復發危險性。
總而言之，nm23-H1蛋白之高度表現可以誘導細胞增殖 (cellular proliferation)，而由低度進展至高度子宮頸鱗狀上皮內病變，並演變成子宮頸鱗狀上皮癌且和癌症基質深度侵犯有關；nm23-H1蛋白並且可以作為癌症預後之標記。

To evaluate the expression of nm23-H1 protein in normal, precancerous and cancerous tissues of the uterine cervix and its role in cervical carcinogenesis, 86 cervical specimens, including 30 squamous cell carcinomas (SCC), 3 adenocarcinomas, one clear cell carcinoma; 19 high- and 13 low-grade squamous intraepithelial lesions (HSILs and LSILs) and 20 normal samples, were stained using an
immunohistochemical method with streptavidin-biotin peroxidase immunostaining. Among the 30 SCC cases, the relationships between immunohistochemical expression of nm23-H1 and various clinicopathological characteristics for early-stage cervical cancer were evaluated. The cumulative recurrence hazard of these patients were also assessed. The Chi-square and Fisher’s exact tests, as well as Chi-square test for trends, were used for comparing nm23-H1 expression among normal, LSIL, HSIL and cancerous tissues. Fisher’s exact test was also used to determine the relationship between nm23-H1 immunoreactivity and the clinicopathologic variables, such as age (≥ 50 or < 50 years old), grade of differentiation (well, moderate or poorly differentiated), depth of stromal invasion ( ≥ 1/2 or < 1/2 of stromal depth), and metastatic status (lymph nodal, parametrial or vaginal variants). Subjects were further subdivided into low and high nm23-H1 expression groups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard. The log-rank test was then used to compare the recurrence distributions for different nm23-H1 expression groups over time. There were significant differences in levels of nm23-H1 expression between LSIL and HSIL (P = 0.016) and between LSIL and SCC (P = 0.002), but not between HSIL and SCC or normal and LSIL samples. Furthermore, a positive relationship was demonstrated for high nm23-H1 protein expression and degree of malignant transformation (P < 0.05). Among various clinicopathological characteristics, only deep stromal invasion ( ≥ 1/2 of stromal depth) was significantly associated with high nm23-H1 expression. Moreover, a high cumulative recurrence hazard was demonstrated for the high nm23-H1 expression group. In conclusion, high nm23-H1 expression may induce the cellular proliferation for the progression from low to high-grade intraepithelial lesions, with the subsequent emergence of invasive carcinoma, as well as deep stromal invasion and be used as a prognostic indicator.

目錄---------------------------------------------------------------------------------1
誌謝---------------------------------------------------------------------------------7
英文摘要---------------------------------------------------------------------------8
中文摘要--------------------------------------------------------------------------10
第一章 緒論-----------------------------------------------------------------------12
1.1 Nm23/nucleoside diphosphate kinase之發現---------------------------12
1.2人類nm23基因家族-------------------------------------------------------13
1.3人類nm23基因家族的作用----------------------------------------------15
1.4子宮頸上皮內贅瘤---------------------------------------------------------16
1.5 Nm23-H1於多種癌症之表現--------------------------------------------17
1.6 Nm23-H1和子宮頸癌化及子宮頸癌臨床病理因子關係之探討--18
第二章 材料與方法------------------------------------------------------------20
2.1樣本及材料------------------------------------------------------------------20
2.2免疫組織化學染色---------------------------------------------------------21
2.3 重要試劑配製--------------------------------------------------------------22
2.4 實驗步驟--------------------------------------------------------------------23
2.5免疫組織化學染色之判讀------------------------------------------------26
2.6統計分析---------------------------------------------------------------------27
第三章 結果---------------------------------------------------------------------28
3.1正常子宮頸nm23-H1蛋白之表現--------------------------------------28
3.2低度和高度子宮頸鱗狀上皮內病變及癌組織nm23-H1蛋白表現28
3.3 Nm23-H1蛋白在正常子宮頸、低度和高度子宮頸鱗狀上皮內病變
及癌組織表現趨勢---------------------------------------------------------29
3.4本研究子宮頸鱗狀上皮癌病例其組織nm23-H1蛋白之表現和臨床
病理特徵之關係------------------------------------------------------------30
第四章 討論---------------------------------------------------------------------31
參考文獻-------------------------------------------------------------------------41
圖 一~十一----------------------------------------------------------------------55
表 一~三-------------------------------------------------------------------------66
表一‧ Nm23-H1蛋白在子宮頸正常鱗狀上皮、低度和高度鱗狀上皮
內病變及癌組織的免疫組織化學表現情形--------------------66
表二‧ Nm23-H1蛋白在子宮頸癌不同組織型態的免疫組織化學表現
情形--------------------------------------------------------------------67
表三‧ 早期子宮頸鱗狀上皮癌病例nm23-H1免疫反應和臨床病理特
徵之關係---------------------------------------------------------------68
附錄--------------------------------------------------------------------------------69
附圖 一‧ 人類Nm23/NDP kinase蛋白家族NDP kinase部分主要結
構之比較 (Reference 13) ---------------------------------------69
附圖二‧ 人類nm23/NDP kinase基因家族系統圖 (Reference 13)---70
附表 一‧ 人類nm23/NDP kinase家族-------------------------------------71
已出版論文------------------------------------------------------------------------72
1. Wang PH, Ko JL, Chang H, Lin LY. Clinical significance of
high nm23-H1 expression in intraepithelial neoplasia and early-stage
squamous cell carcinoma of the uterine cervix. Gynecol Obstet Invest
2003;55:14-19.-----------------------------------------------------------------72
2. Wang PH, Chang H, Ko JL, Lin LY. Nm23-H1 immunohistochemical expression in multisteps of cervical carcinogenesis. Int J Gynecol Cancer 2003;13:325-330.----------------------------------------------------73

1. Berg P, Joklik WK. Transphosphorylation between nucleoside
polyphosphates. Nature 1953;172:1008-1009.
2. Krebs HA, Hems R. Some reactions of adenosine and inosine
phosphates in animal tissues. Biochem Biophys Acta
1953;12:172-180.
3. Cheng YC, Agarwal RP, Parks RE Jr. Erythrocytic nucleoside
diphosphokinase. IV. Evidence for electrophoretic heterogeneity.
Biochemistry 1971;10:2139-2143.
4. Cheng YC, Robison B, Parks RE Jr. Demonstration of the
heterogeneity of nucleoside diphosphokinase in rat tissues.
Biochemistry 1973;12:5-10.
5. Kimura N, Shimada N, Nomura K, Watanabe K. Isolation and
characterization of a cDNA clone encoding rat nucleoside
diphosphate kinase. J Biol Chem 1990;265:15744-15749.
6. Wallet V, Mutzel R, Troll H, Barzu O, Wurster B, Veron M,
Lacombe ML. Dictyostelium nucleoside diphosphate kinase highly
homologous to nm23 and awd proteins involved in mammalian tumor
metastasis and Drosophila development. J Natl Cancer Inst
1990;82:1199-1202.
7. Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta
LA, Sobel ME. Evidence for a novel gene associated with low tumor
metastatic potential. J Natl Cancer Inst 1988;80:200-204.
8. Rosengard AM, Krutzsch HC, Shearn A, Biggs JR, Barker E,
Margulies IM, King CR, Liotta LA, Steeg PS. Reduced Nm23/Awd
protein in tumor metastasis and aberrant Drosophila development.
Nature 1989;342:177-180.
9. Dearolf CR, Hersperger E, Shearn A. Developmental consequences of
awdb3, a cell-autonomous lethal mutation of Drosophila induced by
hybrid dysgenesis. Develop Biol 1988;129:159-168.
10. Biggs J, Tripoulas N, Hersperger E, Dearolf C, Shearn A. Analysis of
the lethal interaction between the prune and Killer of prune
mutations of Drosophila. Genes Develop 1988;2:1333-1343.
11. de la Rosa A, Williams RL, Steeg PS. Nm23/nucleoside
diphosphate kinase: Toward a structural and biochemical
understanding of its biological function. Bioessays 1995;17:53-62.
12. Urano T, Takamiya K, Furukawa K, Shiku H. Molecular cloning and
functional expression of the second mouse nm23/NDP kinase gene,
nm23-M2. FEBS Lett 1992;309:358-362.
13. Lacombe ML, Milon L, Munier A, Mehus JG, Lambeth DO. The
The human nm23/nucleoside diphosphate kinases. J Bioenerg
Biomembr 2000;32:247-258.
14. Stahl JA, Leone A, Rosengard AM, Porter L, King CR, Steeg PS.
Identification of a second human nm23 gene, nm23-H2. Cancer
Res 1991;51:445-449.
15. Gilles AM, Presecan E, Vonica A, Lascu I. Nucleoside diphosphate
kinase from human erythrocytes. Structural characterization of the
two polypeptide chains responsible for heterogeneity of hexameric
enzyme. J Biol Chem 1991;266:8784-8789.
16. Venturelli D, Martinez R, Melotti P, Casella I, Peschle C, Cucco C,
Spampinato G, Darzynkiewiez Z, Calabretta B. Overexpression of
DR-nm23, a protein encoded by a member of the nm23 gene family, inhibits
granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells.
Proc Natl Acad Sci USA 1995;92:7435-7439.
17. Milon L, Rousseau-Merck MF, Munier A, Erent M, Lascu I, Capeau J,
Lacombe ML. nm23-H4, a new member of the family of human
nm23/nucleoside diphosphate kinase genes localized on chromosome
16p13. Human Genet 1997;99:550-557.
18. Lombardi D, Lacombe ML, Paggi MG. Nm23: unraveling its biological
function in cell differentiation. J Cell Physiol 2000;182:144-149.
19. Munier A, Feral C, Milon L, Pinon VP, Gyapay G, Capeau J, Guellaen G,
Lacombe ML. A new human nm23 homologue (nm23-H5) specifically
expressed in testis germinal cells. FEBS Lett 1998;434:289-294.
20. Mehus JG, Deloukas P, Lambeth DO. NME6: a new member of the
nm23/nucleoside diphosphate kinase gene family located on human
chromosome 3p21.3. Human Genet 1999;104:454-459.
21. Tsuiki H, Nitta M, Furuya A, Hanai N, Fujiwara J, Inagaki M, Kochi
M, Ushio Y, Saya H, Nakamura H. A novel human nucleoside
diphosphate (NDP) kinase, Nm23-H6, localizes in mitochondria and
affects cytokinesis. J Cell Biochem 1999;76:254-269.
22. Martinez R, Venturelli D, Perrotti D, Veronese ML, Kastury K, Druck T,
Huebner K, Calabretta B. Gene structure, promoter activity, and
chromosomal location of the DR-nm23 gene, a related member of the nm23
gene family. Cancer Res 1997;57:1180-1187.
23. Amendola R, Martinez R, Negroni A, Venturelli D, Tanno B, Calabretta B,
Raschella G. DR-nm23 gene expression in neuroblastoma cells: relationship
to integrin expression, adhesion characteristics, and differentiation.
J Natl Cancer Inst 1997;89:1300-1310.
24. Fearon ER. Human cancer syndromes: clues to the origin and nature
of cancer. Science 1997;278:1043-1050.
25. Wright Jr TC, Richart RM. Pathogenesis and diagnosis of preinvasive
lesions of the lower genital tract. In: Hoskins WJ, Perez CA, Young RC,
eds. Principles and Practice of Gynecologic Oncology. Philadelphia:
Lippincott-Raven Publishers, 1997:678-680.
26. Bevilacqua G, Sobel ME, Liotta LA, Steeg PS. Association of low nm23
RNA levels in human primary infiltrating ductal breast carcinomas with
lymph-node involvement and other histopathological indicators of high
metastatic potential. Cancer Res 1989;49:5185-5190.
27. Nakayama H, Yasui W, Yokozaki H, Tohara E. Reduced expression of nm23
is associated with metastasis of human gastric carcinomas. JPN J Cancer
Res 1993;84:184-190.
28. Florenes VA, Aamdal S, Myklebost O, Maelansmo GM, Bruland DS ,
Fodstad D. Levels of nm23 messenger RNA in metastatic malignant
melanomas: inverse correlation to disease progression. Cancer Res
1992;52:6088-6091.
29. Engel M, Theisinger B, Seib T, Seitz G, Huwer H, Zang KD, Welter C,
Dooley S. High levels of nm23-H1 and nm23-H2 messenger RNA in human
squamous-cell lung carcinoma are associated with poor differentiation and
advanced tumor stages. Int J Cancer 1993;55:375-379.
30. Myeroff LL, Markowitz SD. Increased nm23-H1 and nm23-H2 messenger
RNA expression and absence of mutations in colon carcinomas of low and
high metastatic potential. J Natl Cancer Inst 1993;85:147-152.
31. Haut M, Steeg PS, Willson JKV, Markowitz SD. Induction of nm23
expression in human colonic neoplasms and equal expression in colon
tumors of both high and low metastatic potential. J Natl Cancer Inst
1991;83:712-716.
32. Zou M, Shi Y, Al-Sedairy S, Farid NR. High levels of nm23 gene
expression in advanced stage of thyroid carcinomas. Br J Cancer
1993;68:385-388.
33. Nakamori S, Ishikawa O, Ohhigashi H, Kameyama M, Furukawa H, Sasaki
Y, Inaji H, Higashiyama M, Imaoka S, Iwanaga T, Funai H, Wada A,
Kimura N. Expression of nucleoside diphosphate kinase/nm23 gene product
in human pancreatic cancer: an association with lymph node metastasis and
tumor invasion. Clin Exp Metastasis 1993;11:151-158.
34. Mandai M, Konishi I, Koshiyama M, Mori T, Arao S, Tashiro H, Okamura
H, Nomura H, Hiai H, Fukumoto M. Expression of metastasis-related
nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with
clinicopathology, EGFR, c-erbB-2, and c-erB-3 genes, and sex steroid
receptor expression. Cancer Res 1994;54:1825-1830.
35. Marone M, Scambia G, Ferrandina G, Giannitelli C, Benedetti-Panici P,
Iacovella S, Leone A, Mancuso S. Nm23 expression in endometrial and
cervical cancer: inverse correlation with lymph node involvement and
myometrial invasion. Br J Cancer 1996;74:1063-1068.
36. Mandai M, Konishi I, Koshiyama M, Komatsu T, Yamamoto S, Nanbu K,
Mori T, Fukumoto M. Altered expression of nm23 H1 and c-erbB-2 proteins
have prognostic significance in adenocarcinoma but not in squamous cell
carcinoma of the uterine cervix. Cancer 1995;75:2523-2529.
37. Kristensen GB, Holm R, Abeler VM, Trope CG. Evaluation of the
prognostic significance of nm23/NDP kinase protein expression in cervical
carcinoma: an immunohistochemical study. Gynecol Oncol 1996;61:378-
383.
38. Lacombe ML, Sastre-Garau X, Lascu I, Vonica A, Wallet V, Thiery
JP, Veron M. Overexpression of nucleoside diphosphate kinase
(nm23) in solid tumors. Eur J Cancer 1991;27:1302-1307.
39. Lee CS, Gad J. nm23-H1 protein immunoreactivity in intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix.
Pathol Int 1998;48:806-811.
40. Weber G, Jackson RC, Williams JC, Goulding FJ, Eberts TJ. Enzymatic
markers of neoplastic transformation and regulation of purine and
pyrimidine metabolism. Adv Enzyme Regul 1977;15:53-77.
41. Ohneda K, Fukuda M, Shimada N, Ishikawa N, Ichou T, Kaji K, Toyota T,
Kimura N. Increased expression of nucleoside diphosphate kinases/nm23 in
human diploid fibroblasts transformed by SV40 large T antigen or 60Co
irradiation. FEBS Lett 1994;348:273-277.
42. Wang PH, Ko JL, Chang H, Lin LY. Clinical significance of high nm23-H1
expression in intraepithelial neoplasia and early-stage squamous cell
carcinoma of the uterine cervix. Gynecol Obstet Invest 2003;55:14-19.
43. Wang PH, Chang H, Ko JL, Lin LY. Nm23-H1 immunohistochemical
expression in multisteps of cervical carcinogenesis. Int J Gynecol Cancer
2003;13:325-330.
44. Ravazoula P, Aletra C, Kourounis G, Ladopoulos I, Tzigounis V.
Immunohistochemical analysis of nm23-H1 expression in human cervical
lesions. Eur J Gynaecol Oncol 2000;21:510-512.
45. de la Rosa A, Williams RL, Steeg PS. Nm23/nucleoside diphosphate kinase:
toward a structural and biochemical understanding of its biological
functions. BioEssays 1995;17:53-62.
46. Keim D, Hailat N, Melhem R, Zhu XX, Lascu I, Veron M, Strahler J,
Hanash SM. Proliferation-related expression of p19/nm23 nucleoside
diphosphate kinase. J Clin Invest 1992;89:919-924.
47. Lee H, Okada K, Baba H, Furukawa K, Chang SI, Shiku H. Intern J Oncol
1997;11:965-970.
48. Sarac E, Ayhan A, Ertoy D, Tuncer ZS, Yasui W, Tahara E, Ayhan A. Nm23
expression in carcinoma of the uterine cervix. Eur J Gynaecol Oncol
1998;19:312-315.
49. Chen HY, Hsu CT, Lin WC, Tsai HD, Chang WC. Prognostic value of
nm23 expression in Stage IB1 cervical carcinoma. JPN J Clin Oncol
2001;31:327-332.
50. Chang CL, Strahler JR, Thoraval DH, Qian MG, Hinderer R, Hanash SM. A
nucleoside diphosphate kinase A (nm23-H1) serine 120 glycine
substitution in advanced stage neuroblastoma affects enzyme stability and
alters protein-protein interaction. Oncogene 1996;12:659-667.
51. Barnes R, Masood S, Barker E, Rosengard AM, Coggin DL, Crowell T,
King CR, Porter-Jordan K, Wargotz ES, Liotta LA, et al. Low nm23 protein
expression in infiltrating ductal breast carcinomas correlates with reduced
patient survival. Am J Pathol 1991;139:245-250.
52. MacDonald NJ, De La Rosa A, Benedict MA, Freije JMP, Krutzsch H,
Steeg PS. A serine phosphorylation of Nm23, and not its nucleoside
diphosphate kinase activity, correlates with suppression of tumor metastatic
potential. J Biol Chem 1993;268:25780-25789.
53. Munoz-Dorado J, Almaula N, Inouye S, Inouye M. Autophosphorylation of
nucleoside diphosphate kinase from Myxococcus xanthus. J Bacteriol
1993;175:1176-1181.
54. Hemmerich S, Pecht I. Oligomeric structure and autophosphorylation of
nucleoside diphosphate kinase from rat mucosal mast cells. Biochemistry
1992;31:4580-4587.
55. Bominaar AA, Tepper AD, Veron M. Autophosphorylation of nucleoside
diphosphate kinase on non-histidine residues. FEBS Lett 1994;353:5-8.
56. MacDonald NJ, Freije JMP, Stracke ML, Manrow RE, Steeg PS.
Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120
abrogates its motility inhibitory activity upon transfection into human breast
carcinoma cells. J Biol Chem 1996;271:25107-25116.
57. Leone A, Flatow U, King CR, Sandeen MA, Margulies IM, Liotta LA,
Steeg PS. Reduced tumor incidence, metastatic potential, and cytokine
responsiveness of nm23-transfected melanoma cells. Cell 1991;65:25-33.
58. Leone A, Flatow U, VanHoutte K, Steeg PS. Transfection of human
nm23-H1 into the human MDA-MB-435 breast carcinoma cell line:
effects on tumor metastatic potential, colonization and enzymatic activity.
Oncogene 1993;8:2325-2333.
59. Kantor JD, McCormick B, Steeg PS, Zetter BR. Inhibition of cell motility
after nm23 transfection of human and murine tumor cells. Cancer Res 1993;
53:1971-1973.
60. Russell RL, Pedersen AN, Kantor J, Geisinger K, Long R, Zbieranski N,
Townsend A, Shelton B, Brunner N, Kute TE. Relationship of nm23 to
proteolytic factors, proliferation and motility in breast cancer tissues and
cell lines. Br J Cancer 1998;78:710-717.
61. Lee HY, Lee H. Inhibitory activity of nm23-H1 on invasion and
colonization of human prostate carcinoma cells is not mediated by its NDP
kinase activity. Cancer Lett 1999;145:93-99.
62. Hsu S, Huang F, Wang L, Banerjee S, Winawer S, Friedman E. The role of
nm23 in transforming growth factor beta 1-mediated adherence and growth
arrest. Cell Growth Differ 1994;5:909-917.
63. Otero AS. Nm23/nucleoside diphosphate kinase and signal transduction. J
Bioenerg Biomembr 2000;32:269-275.
64. Otero AS, Doyle MB, Hartsough MT, Steeg PS. Wild-type NM23-H1, but
not its S120 mutants, suppresses desensitization of muscarinic potassium
current. Biochim Biophys Acta 1999;1449:157-168.
65. Xu L, Murphy J, Otero AS. Participation of nucleoside-diphosphate kinase
in muscarinic K+ channel activation does not involve GTP formation. J Biol
Chem 1996;271:21120-21125.
66. Izumiya H, Yamamoto M. Cloning and functional analysis of the ndk1 gene
encoding nucleoside-diphosphate kinase in Schizosaccharomyces pombe. J
Biol Chem 1995;270:27859-27864.
67. Choi G, Yi H, Lee J, Kwon YK, Soh MS, Shin B, Luka Z, Hahn TR, Song
PS. Phytochrome signalling is mediated through nucleoside diphosphate
kinase 2. Nature 1999;401:610-613.
68. Biggs J, Hersperger E, Steeg PS, Liotta LA, Shearn A. A Drosophila gene
that is homologous to a mammalian gene associated with tumor metastasis
codes for a nucleoside diphosphate kinase. Cell 1990;63:933-940.
69. Otero AS. Copurification of vimentin, energy metabolism enzymes, and a
MER5 homolog with nucleoside diphosphate kinase. Identification of
tissue-specific interactions. J Biol Chem 1997;272:14690-14694.
70. Pinon VP, Millot G, Munier A, Vassy J, Linares-Cruz G, Capeau J, Calvo F,
Lacombe ML. Cytoskeletal association of the A and B nucleoside
diphosphate kinases of interphasic but not mitotic human carcinoma cell
lines: specific nuclear localization of the B subunit. Exp Cell Res
1999;246:355-367.
71. Eckes B, Dogic D, Colucci-Guyon E, Wang N, Maniotis A, Ingber D,
Merckling A, Langa F, Aumailley M, Delouvee A, Koteliansky V, Babinet
C, Krieg T. Impaired mechanical stability, migration and contractile
capacity in vimentin-deficient fibroblasts. J Cell Sci 1998;111:1897-1907.
72. Gilles C, Polette M, Zahm JM, Tournier JM, Volders L, Foidart JM,
Birembaut P. Vimentin contributes to human mammary epithelial cell
migration. J Cell Sci 1999;112:4615-4625.
73. Fedor-Chaiken M, Meigs TE, Kaplan DD, Brackenbury R. Two regions of
cadherin cytoplasmic domains are involved in suppressing motility of a
mammary carcinoma cell line. J Biol Chem 2003;278:52371-52378.
74. Cooper GM. The cell surface. In: Cooper GM, editor. The Cell.
Washington, D.C.: ASM Press, 2000:510-513.
75. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:
57-70.
76. Dusonchet L, Corsale S, Migliavacca M, Calo V, Bazan V, Amato A,
Cammareri P, Totaro MS, Agnese V, Cascio S, La Rocca G, Sisto PS,
Dardanoni G, Valerio MR, Grassi N, Latteri S, Cajozzo M, Buscemi M,
Castorina S, Morello V, Tomasino RM, Gebbia N, Russo A. Nm23-H1
expression does not predict clinical survival in colorectal cancer patients.
Oncol Rep 2003;10:1257-1263.