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標題: 未過度表達HER2之犬乳腺腫瘤細胞株中PTEN之表現
Expression of PTEN in a canine mammary gland tumor cell line with HER2 overexpression
作者: 邱政揚
Chiu, Cheng-Yang
關鍵字: HER2;犬;PTEN;mammary gland tumor;乳腺瘤
出版社: 獸醫學系暨研究所
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磷酯肌醇激酶(phosphatidylinositol 3-kinase, PI3K)/AKT路徑的異常調控,於人類的癌症中被認定為是一種特徵。此路徑的異常表現,於30%以上的癌症病例中被發現。PTEN為一腫瘤抑制基因,功能為負調控磷酯肌醇激酶路徑。磷酯肌醇激酶路徑與細胞的許多重要功能有關,包括代謝、抗凋亡、存活、增殖、生長與移動。本研究主要是在探討人與犬的乳癌細胞株中,PTEN與磷酯肌醇激酶路徑之間的關係。以西方墨點法來比較人類上皮生長因子接受器第2蛋白(HER2)、AKT、磷酸化AKT(pAKT)、與PTEN於犬之乳腺瘤細胞株(DMGT)、未過度表達HER2之人類乳癌細胞株MCF-7與過渡表達HER2的人類乳癌細胞株MCF-7/HER2與MDA-MB-453的表現。以即時聚合酶連鎖反應(real-time PCR)來定量PTEN核醣核酸(RNA)。結果指出在DMGT細胞株中,PTEN蛋白表現的量比MCF-7細胞株低,且磷酸化AKT蛋白表現的量比過度表現HER2的人類乳癌細胞株高。DMGT細胞株PTEN核醣核酸的量比MCF-7細胞株低。並以基因轉殖的方式,借此來觀察PTEN基因在DMGT細胞中對於磷酯肌醇激酶路徑的影響。短暫表現的PTEN會降低磷酸化AKT的表現,比較轉殖前後,DMGT/PTEN具有較高的p53,磷酸化MDM2及細胞週期素D1(cyclin D1)的蛋白表現。於犬未過渡表達HER2的乳腺瘤細胞中,PTEN的低表現可能與癌化有關,且PTEN的表現會影響磷酯肌醇激酶路徑的下游因子表現。

Deregulation of the PI3K signaling pathway is a hallmark of human cancer, perhaps occurring in a majority of tumors. Aberrant PI3K pathway signaling is estimated to be present >30% of human cancer. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that negatively regulates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway that is associated with lots of important cell process functions including metabolism, anti-apoptosis, survival, proliferation, growth, and migration.
We studied the relationship between PTEN and the PI3K pathway in the human and canine mammary gland tumor cell lines. The canine mammary gland tumor cell line (DMGT) was compared the human epidermal growth factor 2 (HER2), AKT, phoshorylated AKT (pAKT), and PTEN protein expression by western blotting with human breast cancer cell line with HER2 (MCF-7/HER2, MDA-MB-453) and without HER2 (MCF-7) overexpression. Real-time PCR was used to quantitate the mRNA of PTEN. Results showed that DMGT has lower expression of PTEN than MCF-7. DMGT showed high expression of pAKT comparing with human breast cancer cell lines with HER2 expression. The quanity of PTEN mRNA in DMGT is lower than MCF-7. The PTEN gene is transfected to the DMGT cells and observe the affection of the PI3K pathway. The transient expression of PTEN down-regulates the expression of pAKT. DMGT/PTEN has higher protein level of p53, pMDM2, and cyclin D1 than DMGT. The low expression of PTEN may be associated with the carcinogensis of the canine mammary tumor without HER2 overexpression. The expression of PTEN affects the downstream signaling factors of PI3K pathway
其他識別: U0005-2107200914431300
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