Furuya Y, Isaacs J T
Johns Hopkins Oncology Center, Baltimore, Maryland.
Endocrinology. 1993 Dec;133(6):2660-6. doi: 10.1210/endo.133.6.8243289.
By manipulating the circulating blood level of androgen, it is possible to induce either the programmed death (apoptosis) or proliferation of prostatic glandular cells. To examine the role of differential gene regulation in these two procedure, the expression of the mRNA of a series of genes was quantitated on a per cell basis during the androgen ablation-induced programmed death of rat prostatic glandular cells. These results were then compared to quantitative analysis of the mRNA expression of these same series of genes during the proliferative regrowth of prostatic glandular cells induced in rats castrated for 1 week before being treated with exogenous androgen replacement. These comparisons demonstrated that androgen ablation-induced programmed death of prostatic glandular cells share several (i.e. c-myc, H-ras, and tissue transglutaminase), but not most, of the epigenetic changes associated with androgen-stimulated proliferation of these cells. No enhancement of the mRNA expression of several genes required for entrance of prostatic glandular cells into the S-phase of the proliferative cycle (i.e. histone-H4, c-fos, p53, and ornithine decarboxylase) occurred during androgen ablation-induced programmed death of these cells. These results demonstrated that neither entrance into the S-phase nor progression through a defective proliferative cell cycle is involved in androgen ablation-induced programmed death of prostatic glandular cells. This was further supported by the observation that there is a set of genes (i.e. TRPM-2, transforming growth factor-beta 1, alpha-prothymosin, and calmodulin) in which mRNA expression is only enhanced during programmed cell death and not during proliferation of prostatic glandular cells induced by androgen replacement. These results demonstrate that prostatic programmed cell death is a distinct pathway from cell proliferation involving differential gene regulation.
通过调控雄激素的循环血液水平，有可能诱导前列腺腺细胞的程序性死亡（凋亡）或增殖。为了研究差异基因调控在这两个过程中的作用，在雄激素去除诱导的大鼠前列腺腺细胞程序性死亡期间，对一系列基因的mRNA表达进行了单细胞水平的定量分析。然后将这些结果与在给予外源性雄激素替代治疗前阉割1周的大鼠中，前列腺腺细胞增殖性再生期间相同系列基因的mRNA表达定量分析结果进行比较。这些比较表明，雄激素去除诱导的前列腺腺细胞程序性死亡与这些细胞雄激素刺激增殖相关的一些（即c-myc、H-ras和组织转谷氨酰胺酶）但不是大多数表观遗传变化相同。在这些细胞雄激素去除诱导的程序性死亡期间，前列腺腺细胞进入增殖周期S期所需的几个基因（即组蛋白-H4、c-fos、p53和鸟氨酸脱羧酶）的mRNA表达没有增强。这些结果表明，前列腺腺细胞雄激素去除诱导的程序性死亡既不涉及进入S期，也不涉及通过有缺陷的增殖细胞周期的进展。这一观点得到了进一步支持，即存在一组基因（即瞬时受体电位阳离子通道亚家族M成员2、转化生长因子-β1、α-原胸腺素和钙调蛋白），其mRNA表达仅在程序性细胞死亡期间增强，而在雄激素替代诱导的前列腺腺细胞增殖期间未增强。这些结果表明，前列腺程序性细胞死亡是一条与涉及差异基因调控的细胞增殖不同的途径。
