Limaye Anil M, Asangani Irfan, Kalyani Thyagarajan, Kondaiah Paturu
Chromatin Biology Lab, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 064, India.
J Biosci. 2008 Jun;33(2):209-20. doi: 10.1007/s12038-008-0038-3.
Involution of the rat ventral prostate and concomitant modulation of gene expression post-castration is a well- documented phenomenon. While the rat castration model has been extensively used to study androgen regulation of gene expression in the ventral prostate,it is not clear whether all the gene expression changes post-castration are due to androgen depletion alone. To obtain insights into this, we performed differential display reverse transcriptase polymerase chain reaction (DD-RT-PCR) which resulted in the identification of castration and/or flutamide-regulated genes in the rat ventral prostate. These include clusterin, methionine adenosyl transferase II alpha, and prostate-specific transcripts such as PBPC1BS, S100RVP and A7. While clusterin, PBPC1BS and methionine adenosyl transferase II alpha are regulated by both castration and flutamide, S100 RVP and A7 are regulated by castration alone. Interestingly, we show that flutamide, unlike castration, does not induce apoptosis in the rat ventral prostate epithelium, which could be an underlying cause for the differential effects of castration and flutamide treatment. We propose that castration leads to enrichment and depletion of stromal and epithelial cell types, respectively, resulting in erroneous conclusions on some of the cell type-specific transcripts as being androgen regulated.
大鼠去势后腹侧前列腺的退化以及伴随的基因表达调节是一个有充分文献记载的现象。虽然大鼠去势模型已被广泛用于研究雄激素对腹侧前列腺基因表达的调节,但尚不清楚去势后所有的基因表达变化是否仅由雄激素耗竭引起。为了深入了解这一问题,我们进行了差异显示逆转录聚合酶链反应(DD-RT-PCR),结果鉴定出了大鼠腹侧前列腺中受去势和/或氟他胺调节的基因。这些基因包括簇集素、甲硫氨酸腺苷转移酶IIα以及前列腺特异性转录本,如PBPC1BS、S100RVP和A7。虽然簇集素、PBPC1BS和甲硫氨酸腺苷转移酶IIα受去势和氟他胺的共同调节,但S100RVP和A7仅受去势调节。有趣的是,我们发现与去势不同,氟他胺不会诱导大鼠腹侧前列腺上皮细胞凋亡,这可能是去势和氟他胺治疗产生不同效果的潜在原因。我们提出,去势分别导致基质细胞和上皮细胞类型的富集和耗竭,从而导致对一些细胞类型特异性转录本受雄激素调节得出错误结论。