ISOLATION AND CHARACTERIZATION OF TRANSCRIPTS INDUCED BY ANDROGEN WITHDRAWAL AND APOPTOTIC CELL-DEATH IN THE RAT VENTRAL PROSTATE

ISOLATION AND CHARACTERIZATION OF TRANSCRIPTS INDUCED BY ANDROGEN WITHDRAWAL AND APOPTOTIC CELL-DEATH IN THE RAT VENTRAL PROSTATE
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DOI:
10.1210/mend-5-10-1381
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发表时间:
1991-10-01
影响因子:
--
通讯作者:
MIESFELD, RL
MIESFELD, RL
中科院分区:
医学2区
文献类型:
--
作者:
BRIEHL, MM;MIESFELD, RL

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已经鉴定了在特定靶细胞中启动转录依赖性程序性细胞死亡(凋亡)的多种刺激。 由于雄激素的撤回诱导大鼠腹侧前列腺(RVP)上皮细胞的退化和凋亡,它是已知的雄激素受体是一种转录调节因子,我们使用减法cDNA克隆分离差异表达的转录本雄激素消融大鼠的RVP。 除了硫酸化糖蛋白-2和谷胱甘肽S-转移酶(GST),这是以前描述的,其他几个转录被发现是升高3至8倍,在回归RVP。 DNA测序显示,这些cDNA克隆编码基质羧基谷氨酸和γ-肌动蛋白,分别。 第三个cDNA包含新的序列信息,被命名为RVP.1。 RVP.1转录物在正常成年大鼠的RVP和附睾中以非常低的水平表达(<总mRNA的0.01%),并且在其他组织(如肾脏、肝脏和肌肉)中检测不到。 RVP.1编码一个推定的280个氨基酸的蛋白质,其与先前描述的蛋白质功能结构域没有显著的同源性。 我们研究了这些转录本在血清饥饿的NIH 3 T3细胞中的表达,以确定它们中的任何一个在生长停滞的细胞中是否升高。 发现在这些条件下仅GST mRNA水平增加。 这些数据可能表明,诱导某些基因,如RVP.1,可能与细胞凋亡,而其他转录,如GST,可能是上调响应改变细胞代谢率。
A variety of stimuli have been identified which initiate transcription-dependent programmed cell death (apoptosis) in specific target cells. Since the withdrawal of androgens induces regression and apoptosis in rat ventral prostate (RVP) epithelial cells, and it is known that the androgen receptor is a transcriptional regulator, we used subtraction cDNA cloning to isolate differentially expressed transcripts from the RVP of androgen ablated rats. In addition to sulfated glycoprotein-2 and glutathione S-transferase (GST), which had been previously described, several other transcripts were found to be elevated 3- to 8-fold in the regressing RVP. DNA sequencing revealed that two of these cDNA clones encode matrix carboxyglutamic acid and gamma-actin, respectively. A third cDNA contained novel sequence information and was named RVP.1. The RVP.1 transcript is expressed at very low levels in the RVP and epididymis of normal adult rats (< 0.01% of the total mRNA) and is undetectable in other tissues, such as kidney, liver, and muscle. RVP.1 encodes a putative 280-amino acid protein, which shares no significant homology with previously described protein functional domains. We examined the expression of these transcripts in serum-starved NIH 3T3 cells to determine whether any of them are elevated in cells that are growth arrested. It was found that only GST mRNA levels are increased under these conditions. These data may suggest that induction of some genes, such as RVP.1, could be associated with apoptosis, whereas other transcripts, such as GST, may be up-regulated in response to altered rates of cellular metabolism.