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研究生:蕭瑞康
研究生(外文):Jui-kang Hsiao
論文名稱:乳突狀甲狀腺癌中Akt和JNK蛋白質過度表現與Erk1/2蛋白質低磷酸化有關
論文名稱(外文):Overexpression of Akt and JNK associated with low phosphorylation of Erk1/2 in papillary thyroid carcinoma
指導教授:湯銘哲湯銘哲引用關係
指導教授(外文):Ming-jer Tang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:英文
論文頁數:62
中文關鍵詞:乳突狀甲狀腺癌訊息傳遞受體酪氨酸激化脢
外文關鍵詞:papillary thyroid carcinomaAktJNKErk1/2RETsignal transductionreceptor tyrosine kinase
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乳突狀甲狀腺癌是最常見的濾泡細胞衍生性甲狀腺癌,形成原因常是經由ret原致癌基因藉著染色體重組形成一個基因置換過之ret(rearranged RET,RET/PTC)並且能持續活化所造成。RET(Rearrangement induced transformation)是一種受體酪氨酸激化脢(receptor tyrosine kinase),參與腎臟及腸道神經系統之發育並和腫瘤的形成有關。目前對乳突狀甲狀腺癌是否有對於正常之RET(wild-type RET)表現並不清楚。在此研究之中,我們收集了27例乳突狀甲狀腺癌以及8例正常甲狀腺組織。為了研究在乳突狀甲狀腺癌生成過程之訊息傳遞路徑,我們分析了幾個RET訊息傳遞路徑下游之訊息傳遞蛋白質的表現及磷酸化,例如:Akt、JNK、Erk1/2 以及p85。有趣的是,我們發現Akt和JNK在乳突狀甲狀腺癌的蛋白質表現明顯高於正常甲狀腺組織,然而Akt和JNK的磷酸化比率卻沒有差異。相反地,Erk1/2在乳突狀甲狀腺癌的磷酸化程度明顯低於正常甲狀腺組織。因此在乳突狀甲狀腺癌之中所發現不尋常的高度Akt和JNK的蛋白質表現,可能和乳突狀甲狀腺癌的病理形成機制有關。此外我們發現Akt的蛋白質表現和Erk1/2的蛋白質磷酸化的關係呈現負相關,顯示在乳突狀甲狀腺癌之中,Akt的蛋白質過度表現及活化現象可能抑制了Erk1/2蛋白質的磷酸化。
為了找出在乳突狀甲狀腺癌之中,造成Akt和JNK的高蛋白質表現之調節機制,我們以反轉錄聚合脢連鎖反應(RT-PCR)的方法分析了Akt及JNK的mRNA表現情形。結果顯示在乳突狀甲狀腺癌與正常甲狀腺組織,其Akt及JNK的mRNA表現情形並沒有差異,所以Akt和JNK的高蛋白質表現之調節可能和轉錄之後的機制有關。我們也以反轉錄聚合脢連鎖反應(RT-PCR)的方法分析了在乳突狀甲狀腺癌正常的RET之mRNA表現情形,發現88.8%的乳突狀甲狀腺癌都有表現,顯示在乳突狀甲狀腺癌之中,其正常的RET之mRNA表現,可能在形成乳突狀甲狀腺癌的病理機制過程中扮演重要角色。

Papillary thyroid carcinomas (PTC) is the most common follicular cell-derived thyroid cancer which is often caused by somatical rearrangement of ret gene that results in a constitutive activation of rearranged RET. Rearrangement induced transformation (RET) is a receptor tyrosine kinase involved in the development of kidney and enteric nervous system and associated with several neoplasia. Whether RET expression in PTC is elevated is not certain yet. We collected 27 cases of PTCs and 8 cases of normal thyroid. To delineate signal pathways in formation of PTC, we analyzed expression and phosphorylation of several signal proteins in downstream of RET, such as Akt and JNK, Erk1/2, and p85. We observed that levels of Akt and JNK were significantly higher in PTC than in normal thyroid tissue. However, the phosphorylation/expression ratio of Akt and JNK were not different between normal thyroid tissue and PTC. In contrast, the phosphorylation/expression ratio of Erk1/2 was markedly lower in PTC than normal thyroid tissue. Therefore, abnormally high expression of Akt and JNK in PTCs might be associated with the pathogenesis of PTC. Furthermore, there was an inverse correlation between Akt levels and phospho-Erk1/2, indicating that overexpression and activation of Akt may inhibit phosphorylation of Erk1/2 in PTC.
To clarify the regulating mechanisms involved in higher expression of Akt and JNK in PTCs, mRNA of Akt and JNK was assessed by RT-PCR. The results showed that Akt and JNK isoforms between normal thyroid tissue and PTC were not different. The up-regulation of Akt and JNK in PTC might be regulated at post-transcriptional level. We also analyzed the expression of wild-type RET in PTC and normal thyroid by RT-PCR. Wild-type RET mRNA seemed to be augmented in PTC, suggesting that the expression of wild-type RET mRNA might be important in pathogenesis of PTC.

Abstract………………………… I
中文摘要……………………….. III
誌謝…………………………….. V
Content………………………… VI
Figure content…………………. VII
Introduction…………………… 1
Materials and methods……….. 5
Results…………………………. 13
Discussion……………………… 20
References……………………… 25
Figures
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