Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

作     者：Jun Chen Dan Xia Jin-Dan Luo Ping Wang 

作者机构：Department of Urology The First Affiliated Hospital Medical College of ZheJiang University Hangzhou 310003 China 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2009年第11卷第6期

页      面：669-677页

核心收录：

学科分类：0710[理学-生物学] 090601[农学-基础兽医学] 1002[医学-临床医学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0906[农学-兽医学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

主　　题：apoptosis EGFR p27 prostate cancer cells signalling pathway 

摘      要：p27 is a cyclin-dependent kinase inhibitor that regulates the progression of cells from G1 to S phase of the cell cycle. Loss of p27 has been associated with disease progression and with an unfavourable outcome in prostate cancer. In this study, we investigated whether exogenous p27 expression in the human androgen-independent prostate cancer PC3 cell line had any effect on cell growth, and we studied the molecular mechanisms involved. p27 expression was restored in PC3 cells by plasmid delivery. Cell proliferation and apoptosis were assessed in PC3 cells transfected with p27. We also investigated the effects of p27 on the epidermal growth factor receptor （EGFR）/ phosphatidylinositol 3-kinase （PI3K）/Akt signalling pathway in PC3 cells. By restoring p27 expression in PC3 cells, we observed that p27 reduced proliferation and induced arrest in G0/G1 phase. Moreover, p27-transfected PC3 cells underwent apoptosis, as shown by flow cytometric analysis and western blotting analysis of Bcl-2, Bax, Bad, caspase-3 and poly（ADP-ribose）polymerase expression. Furthermore, the p27-induced anti-tumour action corre- lated with inhibition of the EGFR/PI3K/Akt signalling pathway, as confirmed by western blotting analysis and densitometry of EGFR, PI3K （p85）, Akt and p-Akts473 expression. Our results suggest that exogenous expression of p27 inhibits the proliferation of PC3 cells through induction of G1 arrest and apoptosis, and this process correlates with inhibition of the EGFR/PI3K/Akt signalling pathway.