人前列腺癌细胞系PC-3再表达雄激素受体(AR)的肿瘤生物学特性研究及其意义  

Biological behaviors of human prostate cancer cells PC-3-AR^+with androgen receptor(AR)-overexpressed and its significance

作　　者：刘欣[1,2] 曹靖晨 王海燕[3] 鄂群[3,4] 张冲[3] 张永辉[3] 陈苗苗[3] 顾晓[2] 江明[3] 

机构地区：[1]江苏省靖江市人民医院泌尿外科,靖江214500 [2]江苏省苏北人民医院泌尿外科 [3]南通大学医学院基础医学研究室核受体与肿瘤研究实验室 [4]南通大学医学院病理学系

出　　处：《中国男科学杂志》2015年第7期6-13,共8页Chinese Journal of Andrology

基　　金：国家自然科学基金(NSFC)面上项目(项目批准号:81372772);江苏特聘教授科研基金(苏教师【2012】34号)

摘　　要：目的研究人全长雄激素受体（androgen receptor, AR）cDNA质粒（pSAR-IRES—EGFP）在人进展期前列腺癌细胞系PC-3中稳转染再表达，即人前列腺癌细胞系PC-3-AR＋的肿瘤生物学特性及其干细胞相关基因蛋白表达的变化，探讨AR的分子生物学作用。方法（1）应用体外细胞培养，通过四氮甲基唑氮（MTT）和细胞划痕等方法检测癌细胞生长和迁移特性；WesternBlot方法检测干细胞相关蛋白的表达；细胞爬片和免疫荧光方法检测干细胞相关蛋白的定位和表达。（2）应用人前列腺癌细胞组织重组．先天免疫缺陷小鼠（Nude）肾包膜下移植技术，建立人前列腺癌．小鼠移植瘤模型，通过H.E．染色和病理学分析研究癌细胞的成瘤性、浸润和转移能力等肿瘤生物学特性；通过免疫组化染色技术检测移植瘤干细胞相关蛋白的定位和表达。结果人雄激素非依赖型进展期前列腺癌细胞系PC-3再表达全长ARcDNA，IPPC-3-AR＋，导致以下情况的改变：（1）体外细胞培养中癌细胞的生长和扩增能力以及迁移特性均受抑制；（2）小鼠体内移植瘤肿瘤体积减小，癌细胞变大，分化增强，坏死增加和浸润能力减低；（3）培养细胞中检测到干细胞相关蛋白CD133、CD44和ALDH等的表达增加。结论人雄激素非依赖型前列腺癌细胞系PC．3再表达全长ARcDNA，使其生长受抑，分化增强，坏死增加和干细胞相关基因蛋白（CD133、CD44和ALDH）的表达增加。Objective To investigate the changes of biological behaviors and stemness-related gene expression levels in human prostate cancer cells PC-3-AR＋ with androgen receptor （AR）-overexpressed and discuss its possible functionMethods （1） Cancer cell growth and migration were respectively measured by MTT assay and wound healing assay, The expressions of stemness-related proteins were detected by Western blot. The expression pattern and localization of stemness-related proteins were detected by cell immunofluerescence staining. （2） The human prostate cancer xenografting mouse models were established to detect the expression pattern and localization of sternness-related proteins and analyze histopathological changes. The models were established by implanting the tissue recombinants into the sub-renal capsule of severe combined immunodeficient （Nude） mice. Results Overexpression of full-length androgen receptor （AR） in human prostate cancer cell line PC-3-AR＋ could lead to the following results. （1） The characteristics of cell growth and migration were inhibited; （2） The differentiation ability of xenografted cancer cells was increased, the tumor size and invasion ability were decreased. （3） The expression levels of stemness-related proteins, such as CD133, CD44 and ALDH, were enhanced. Conclusion The overexpression of full-length AR cDNA in human prostate cancer cells may result in the changes of cancer biological behaviors and steumess-related proteins expression.

关 键 词：前列腺肿瘤 细胞系 肿瘤 受体 雄激素 干细胞相关基因 

分 类 号：R737.25[医药卫生—肿瘤]