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人类同源框cDNA NKX3.1的分离及雄激素调控

Isolation and androgen regulation of the human homeobox cDNA, NKX3.1.

作者信息

Prescott J L, Blok L, Tindall D J

机构信息

Department of Biochemistry, Mayo Foundation, Rochester, Minnesota 55905, USA.

出版信息

Prostate. 1998 Apr 1;35(1):71-80. doi: 10.1002/(sici)1097-0045(19980401)35:1<71::aid-pros10>3.0.co;2-h.

DOI:10.1002/(sici)1097-0045(19980401)35:1<71::aid-pros10>3.0.co;2-h
PMID:9537602
Abstract

BACKGROUND

The prostate is dependent on androgens for development and maintenance of its differentiated phenotype. We have applied the technique of differential display PCR to the androgen-sensitive prostate cancer cell line LNCaP to isolate androgen-responsive genes.

METHODS

The technique of DD-PCR was applied to androgen-stimulated LNCaP cell RNA to detect and isolate androgen-responsive genes.

RESULTS

The human homeobox gene NKX3.1, the homologue to mouse Nkx3.1, recently isolated by Beiberich et al. [J Biol Chem 1996;271:31779-31782], was detected and cloned. NKX3.1 is induced by androgens in a time- and concentration-dependent manner. NKX3.1 is induced 6- to 7-fold in 12 hr, with a significant induction seen in 2 hr. This regulation is at the level of transcription, as androgens increase the number of new NKX3.1 transcripts, and de novo protein synthesis is not required. In humans, NKX3.1 is expressed most highly in the prostate, with a much lower level of expression seen in the testis. No other tissue examined showed detectable levels of NKX3.1 expression.

CONCLUSIONS

NKX3.1 is an androgen-regulated, prostate-specific homeobox gene. We hypothesize that it may play a role in the development and differentiation of the prostate.

摘要

背景

前列腺的发育和分化表型的维持依赖雄激素。我们应用差异显示PCR技术,对雄激素敏感的前列腺癌细胞系LNCaP进行研究,以分离雄激素反应基因。

方法

应用差异显示PCR技术检测雄激素刺激的LNCaP细胞RNA,以检测和分离雄激素反应基因。

结果

检测并克隆了人同源盒基因NKX3.1,它是小鼠Nkx3.1的同源物,最近由Beiberich等人分离得到[《生物化学杂志》1996年;271:31779 - 31782]。NKX3.1以时间和浓度依赖性方式被雄激素诱导。在12小时内,NKX3.1被诱导6至7倍,在2小时时就可见明显诱导。这种调节发生在转录水平,因为雄激素增加了新的NKX3.1转录本数量,且不需要从头合成蛋白质。在人类中,NKX3.1在前列腺中表达最高,在睾丸中的表达水平则低得多。所检测的其他组织均未显示出可检测到的NKX3.1表达水平。

结论

NKX3.1是一种雄激素调节的、前列腺特异性的同源盒基因。我们推测它可能在前列腺的发育和分化中起作用。

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