Molecular mechanisms of androgen-independent growth of human prostate cancer LNCaP-AI cells
Molecular mechanisms of androgen-independent growth of human prostate cancer LNCaP-AI cells
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DOI：
10.1210/en.140.11.5054
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发表时间：
1999-11-01
期刊：
影响因子：
4.8
通讯作者：
Tsai, MJ
中科院分区：
文献类型：
--
作者：
Lu, S;Tsai, SY;Tsai, MJ
本研究的目的是探讨前列腺癌中雄激素非依赖性生长的分子机制。我们从雄激素依赖性LNCaP- fgc细胞中建立了雄激素非依赖性前列腺癌LNCaP- ai（定义为能够在炭剥离血清中生长的LNCaP细胞系）。与雄激素不依赖型PC-3人前列腺癌细胞相比，LNCaP-AI细胞表达的雄激素受体水平与亲本细胞相近，且对雄激素刺激敏感。与亲本LNCaP-FGC细胞相比，LNCaP-AI细胞对12-O-tetradecanoylphorbol- 13-acetate诱导的凋亡具有更强的抗性，并且表达更高水平的抗凋亡基因bcl-2和细胞周期蛋白依赖性激酶抑制剂p21，这可能赋予了增强的抗凋亡表型。另一方面，细胞周期蛋白依赖性激酶抑制剂p16在LNCaP-AI细胞中的表达显著降低，这意味着p16对细胞周期进程的抑制作用得以释放。综上所述，我们的研究结果表明，多种因素促进了前列腺癌细胞雄激素非依赖性生长的发展，包括细胞抗凋亡功能的增强，细胞周期抑制的释放，以及通过其他信号通路刺激细胞增殖。
The goal of this study is to investigate the molecular mechanisms of androgen-independent growth in prostate cancer. We have established an androgen-independent prostatic carcinoma LNCaP-AI (defined as a LNCaP cell Line that is capable of growing in charcoal-stripped serum) from the androgen-dependent LNCaP-FGC cells. In contrast to the androgen-independent PC-3 human prostate cancer cells, LNCaP-AI cells still express a similar level of androgen receptor as their parental cells and are sensitive to androgen stimulation. Compared with the parental LNCaP-FGC cells, LNCaP-AI cells are more resistant to apoptosis induced by 12-O-tetradecanoylphorbol- 13-acetate and express a much higher level of antiapoptotic gene bcl-2 and cyclin-dependent kinase inhibitor p21, which may confer an enhanced antiapoptosis phenotype. On the other hand, expression of cyclin-dependent kinase inhibitor p16 is significantly reduced in the LNCaP-AI cells, implying the release of an inhibitory effect of p16 on cell cycle progression. Taken together, our results suggest that multiple factors contribute to the development of androgen-independent growth of prostatic carcinoma cells, including enhancement of cell antiapoptosis function, release of cell cycle inhibition, and stimulation of cell proliferation by alternative signaling pathways.