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首页> 外文期刊>Journal of Cellular Physiology >Activation of Rb and decline in androgen receptor protein precede retinoic acid-induced apoptosis in androgen-dependent LNCaP cells and their androgen-independent derivative.
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Activation of Rb and decline in androgen receptor protein precede retinoic acid-induced apoptosis in androgen-dependent LNCaP cells and their androgen-independent derivative.

机译：雄激素受体激活Rb和下降蛋白质之前视黄段细胞凋亡在androgen-dependent LNCaP细胞和他们的androgen-independent导数。

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摘要

Androgen ablation-induced prostate cancer regression is transient and ends with the regrowth of androgen-independent (AI) tumors. To mimic this evolution in culture, we chronically deprived an androgen-dependent (AD) prostate cancer cell line (LNCaP) of androgen, generating an AI derivative which retained limited hormone proliferative responsiveness and a barely detectable prostate-specific antigen (PSA) mRNA level. While the cytokeratin 8 (CK8) level was low, the androgen receptor (AR) protein in AI cells was on average tenfold greater than in AD cells. When challenged for susceptibility to undergo apoptosis, the AI cells were more resistant than AD cells to all-trans retinoic acid (tRA) and two chemotherapeutic agents, Taxol and Adriamycin, requiring higher doses and longer periods of treatment to achieve similar effects. Compared to AD cells, the partially apoptosis-resistant AI cells expressed four times more Bcl-2 protein and undetectable levels of p21/WAF1. Induction of apoptosis by tRA in both cell types did not affect their expression but was preceded by the activation of Rb and a pronounced reduction of AR protein level. The kinetics of the Rb activation and AR downmodulation in both cell types matched their tRA sensitivity, suggesting that these events may be required for tRA-induced apoptosis. The results show that the apoptotic pathway in AI cells, although more difficult to induce, is not irrevocably lost and that targeted reduction of the AR protein level with retinoids in combination with androgen ablation therapy may prolong remissions in advanced prostate cancer patients.
机译：前列腺癌雄激素ablation-induced回归是瞬态和结束再生的androgen-independent (AI)肿瘤。模仿文化的演变,我们长期剥夺了一个androgen-dependent(广告)前列腺癌癌症细胞系(LNCaP)雄激素的产生一个AI导数保留有限的激素增生性反应和勉强检测前列腺特异性抗原(PSA) mRNA的水平。低,人工智能的雄激素受体(AR)的蛋白质细胞平均10倍大于广告细胞。进行细胞凋亡,AI细胞更多耐药细胞比广告all-trans视黄酸(交易)和两个化疗药物,紫杉醇和阿霉素,要求更高的剂量和更长的期的治疗达到类似的效果。广告细胞相比,部分apoptosis-resistant AI细胞表达了四次更多的bcl - 2蛋白和检测水平p21 / WAF1。但细胞类型并不影响他们的表达式之前是Rb和激活吗AR蛋白水平的明显减少。Rb激活动力学和基于“增大化现实”技术downmodulation在两种细胞类型匹配他们的交易的敏感性,这表明这些事件tRA-induced所需细胞凋亡。结果表明,人工智能的凋亡途径细胞,尽管更难诱导,不是不可挽回的损失,有针对性的减少类维生素a的基于“增大化现实”技术的蛋白质水平结合可能接受雄激素阻断疗法延长缓解晚期前列腺癌病人。

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