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作 者:俞岚[1] 施庆国[1] 钱晓龙[1] 李山虎[1] 王洪涛[1] 王乐乐[1] 周建光[1]
机构地区:[1]军事医学科学院生物工程研究所,北京100850
出 处:《遗传》2010年第4期348-352,共5页Hereditas(Beijing)
基 金:国家自然科学基金项目(编号:30770834;30870961);国家高技术研究发展计划项目(编号:2008AA02Z123)资助
摘 要:前列腺癌相关基因PC-1(Prostate and colon gene1)是属于癌基因D52家族成员,具有促进前列腺癌细胞雄激素非依赖性生长的功能。为了研究PC-1发挥这种生物功能的分子机制,文章在PC-1高表达的LNCaP-pc-1及对照LNCaP-zero细胞中,利用RT-PCR和Western blotting等方法检测c-myc基因表达;提取两细胞胞质和胞核蛋白,利用Western blotting分析c-myc上游调节蛋白β-catenin变化;利用c-Myc蛋白抑制剂10058-F4作用前列腺癌细胞C4-2,Western blotting检测PC-1蛋白表达变化。发现PC-1促进c-myc基因表达,并促进β-catenin入核;c-Myc蛋白抑制剂10058-F4可抑制PC-1的表达。结果表明:PC-1在前列腺癌中促进c-myc基因的表达,并且这种促进作用可能是通过Wnt/β-catenin信号通路实现的。同时,PC-1与c-Myc蛋白间可相互促进,进一步促进前列腺癌细胞雄激素非依赖性生长。PC-1(Prostate and colon gene 1)gene belongs to TPD52(Tumor Protein D52)gene family.The expression of PC-1 is found to promote androgen-independent progression.This study was conducted to assess the mechnism of promotion of androgen-independent progression in PC-1 gene.The c-myc gene expression was tested by RT-PCR and Western blotting analyses in the LNCaP-pc-1 and LNCaP-zero cell line.After separation of cytoplasm and nulear proteins of the LNCaP-pc-1 and LNCaP-zero cell line,theβ-catenin protein was detected by Western blotting.C4-2 cell line was used to examine the effects of 10058-F4 on the PC-1 gene expression.The results of RT-PCR and Western blotting indicated that PC-1 enhanced c-myc gene expression in prostate cancer cells,PC-1 was also found to enhanceβ-catenin expression in nuclear.Furthermore,a small-molecule c-Myc inhibitor,10058-F4 represses PC-1 gene expression in C4-2 cell line.Our findings suggest that PC-1 enhances c-myc gene expression in prostate cancer cells through the Wnt/β-catenin pathway. Meanwhile,c-myc plays a feed-forward role in enhancing PC-1 driven c-myc gene expression,and promotes prostate androgen-independent progression.
关 键 词:前列腺癌 前列腺癌相关基因(PC-1) C-MYC基因 Β-CATENIN蛋白
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