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Up-regulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage

机译:Bcl-2的上调是前列腺癌细胞从雄激素依赖性生长到非雄激素依赖性生长阶段所必需的

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摘要

Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers. However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that Bcl-2 is required for the progression of LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. The mRNA and protein levels of Bcl-2 are significantly increased in androgen-independent prostate cancer cells. shRNA-medi-ated gene silencing of Bcl-2 in androgen-independent prostate cancer cells promotes UV-induced apoptosis and suppresses the growth of prostate tumors in vivo. Growing androgen-dependent cells under androgen-deprivation conditions results in formation of androgen-independent colonies; and the transition from androgen-dependent to androgen-independent growth is blocked by ectopic expression of the Bcl-2 antagonist Bax or Bcl-2 shRNA. Thus, our results demonstrate that Bcl-2 is not only critical for the survival of androgen-independent prostate cancer cells, but is also required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage.
机译:Bcl-2是一种抗凋亡的癌蛋白,其蛋白水平与许多癌症的预后成反比。但是,Bcl-2在前列腺癌进展中的作用尚不清楚。在这里我们报告Bcl-2是LNCaP前列腺癌细胞从雄激素依赖性生长到雄激素非依赖性生长阶段所必需的。在雄激素非依赖性前列腺癌细胞中,Bcl-2的mRNA和蛋白水平显着增加。在雄激素非依赖性前列腺癌细胞中,Bcl-2的shRNA介导的基因沉默可促进紫外线诱导的细胞凋亡并在体内抑制前列腺肿瘤的生长。在雄激素剥夺条件下生长的雄激素依赖性细胞会导致雄激素非依赖性菌落的形成。 Bcl-2拮抗剂Bax或Bcl-2 shRNA的异位表达可阻止从雄激素依赖性生长到非雄激素依赖性生长的转变。因此,我们的结果证明,Bcl-2不仅对于非雄激素依赖性前列腺癌细胞的存活至关重要,而且对于前列腺癌细胞从雄激素依赖性生长到非雄激素依赖性生长阶段也是必需的。

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