ADAM17通过EGFR-PI3K/Akt/p27通路调控前列腺癌细胞增殖  

ADAM17 Regulates Proliferation via the EGFR-PI3K /Akt /p27 Pathway in Prostate Cancer Cells

作　　者：吴琦[1,2] 冯田[1] 孙希财[1] 林平[1] 边淑玲[1] 赵雪飞[1] 李聪[3] 于晓光[1] 

机构地区：[1]哈尔滨医科大学生物化学与分子生物学教研室,哈尔滨150081 [2]齐齐哈尔医学院生物化学与分子生物学教研室,齐齐哈尔161006 [3]哈尔滨医科大学附属肿瘤医院病理科,哈尔滨150081

出　　处：《中国生物化学与分子生物学报》2010年第8期749-755,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No30772173);黑龙江省自然科学基金(NoD2007-56)资助项目~~

摘　　要：ADAM17是金属蛋白酶家族(ADAMs)成员之一,研究发现ADAM17可以通过水解细胞表面蛋白的胞外结构域导致肿瘤细胞的增殖和转移.本课题前期研究结果显示,与LNCap细胞相比,ADAM17在DU145细胞中高表达,且与细胞增殖相关.为了研究ADAM17与前列腺癌细胞增殖相关基因p27表达的关系及调控机制,我们采用RNAi技术下调ADAM17的表达,加入PMA(一种ADAM17的激活剂)上调ADAM17的表达,通过细胞计数和CCK-8方法检测细胞增殖,RT-PCR检测p27mRNA的表达,Western印迹检测ADAM17的表达;进一步阻断EGFR和PI3K/Akt信号转导,RT-PCR方法检测p27mRNA的表达,Western印迹检测ADAM17、EGFR、pEGFR、Akt和pAkt的表达.结果显示ADAM17的表达与前列腺癌细胞的增殖呈正相关(P<0.05);p27mRNA的表达与ADAM17的表达呈负相关(P<0.05);分别阻断EGFR和PI3K/Akt信号转导通路,同时使ADAM17表达增加,与对照组(单独PMA处理组)相比,p27mRNA的表达均增加(P<0.05).提示ADAM17调控前列腺癌细胞增殖相关基因p27表达是通过EGFR-PI3K/Akt信号通路实现的.A disintegrin and metalloproteinase 17 （ADAM17） is a member of the ADAM family leading to tumor proliferation and metastasis by hydrolyzing the ectodomain of diverse cell surface proteins. Our previous findings demonstrated that ADAM17 was more highly expressed in DU145 cells than in LNCap cells and contributed to cell proliferation. To investigate the relationship and regulatory mechanism between ADAM17 and prostate cancer cell proliferation related gene p27 expression,we down-regulated ADAM17 expression by RNAi technology and up-regulated it by PMA （ an activator of ADAM17）. The cell count and CCK-8 assay were used to measure cell proliferation. The expression of p27 mRNA and ADAM17 was detected by RT-PCR and Western blot,respectively. Then after inhibiting the EGFR-PI3K /Akt signaling pathway,we also checked the expression of ADAM17,EGFR,pEGFR,Akt and pAkt by Western blot. Results showed there was a positive correlation between ADAM17 expression and prostate cancer cell proliferation （P〈 0. 05）,but a negative correlation between p27 mRNA and its cell proliferation （P〈 0. 05）. Furthermore,compared with the control （PMA treatment only）,increased p27 mRNA was associated with inhibition of the EGFR-PI3K /Akt signaling pathway （ P〈 0. 05 ）,and ADAM17 expression was up-regulated in both groups at the same time. Altogether,these data suggest that ADAM17 regulate prostate cancer cell proliferation and p27 gene expression via the EGFR-PI3K /Akt pathway.

关 键 词：前列腺癌 ADAM17 pEGFR PAKT P27 

分 类 号：Q71[生物学—分子生物学]