非受體型特異性酪胺酸去磷酸酶23在上皮生長因子受體訊息傳遞之調控角色探討

The regulatory role of PTPN23 on EGFR signaling

陳禹帆(Yu-Fan Chen)

指導教授 ： 陳怡榮 ； 陳令儀

國立清華大學/生命科學院/分子醫學研究所/碩士(2013年)

摘要

非受體型酪胺酸蛋白激酶23(PTPN23)先前文獻已指出具有抑制癌細胞轉移與入侵的能力以及被認為與內吞作用有關。然而，PTPN23對於抑制腫瘤形成的機轉仍然未知。本篇論文以H1299肺癌細胞株作為實驗的模型去闡述PTPN23在肺癌中所可能扮演的角色。實驗結果發現PTPN23會促進tumor necrosis factor (TNF)所誘導的細胞凋亡，並且PTPN23也會降低藉由EGF誘導的EGFR及ERK1/2的磷酸化。根據前述的結果，推測PTPN23可能參與受體的降解作用，然而螢光染色的結果顯示失去PTPN23並沒有影響EGFR的內在化現象。儘管如此，PTPN23在EGFR突變的肺癌細胞株的表現量較正常EGFR肺癌細胞株低，並且也在EGFR突變的轉殖基因鼠中觀察到PTPN23表現量較正常肺部組織有下降的現象。綜合上述實驗結果,推測PTPN23可能在肺癌細胞中藉由調節EGFR與TNFR訊息傳遞路徑作為一個腫瘤抑制者的角色。

關鍵字

肺癌 ； 受體型酪胺酸磷酸酶 ； 表皮生長因子受體 ； 腫瘤壞死因子受體 ； 細胞凋亡

並列摘要

The non-receptor protein tyrosine phosphatase 23 (PTPN23) has been reported to inhibit cancer cell migration and invasion and is involved in the endocytosis process. However, the mechanisms of PTPN23 in blocking tumorgenesis remain unclear. Here, we used lung cancer cell line H1299 as a cell model to elucidate the role of phosphatase PTPN23 in lung cancer. We found that PTPN23 can enhance tumor necrosis factor (TNF)-induced apoptosis. Moreover, PTPN23 also decrease the phosphorylation of epidermal growth factor receptor (EGFR) and ERK1/2 induced by EGF. According to previous data, we suggest PTPN23 is involved the down-regulation of receptor, although our immunofluorescence data show that lose of PTPN23 does not affect receptor internalization. However, lung cancer cells with mutant EGFR showed lower levels of PTPN23 than those with wild type EGFR. Decreasing PTPN23 expression was also observed in lung cancer developed in EGFR mutant-transgenic mice. The collective data suggest that PTPN23 may serve as a tumor suppressor in lung cancer through modulating EGFR and TNFR signaling pathways.

並列關鍵字

Lung cancer ； PTPN23 ； EGFR ； TNFR ； Apoptosis

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