HOXA5 regulates expression of the progesterone receptor
HOXA5 regulates expression of the progesterone receptor
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DOI：
10.1074/jbc.c000324200
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发表时间：
2000-08-25
影响因子：
4.8
通讯作者：
Sukumar, S
中科院分区：
文献类型：
--
作者：
Raman, V;Tamori, A;Sukumar, S
大多数乳腺癌显示转录因子HOXA 5的表达减少或不表达。最近，我们已经表明HOXA 5是乳腺细胞中p53的有效反式激活因子，因此可能影响乳腺癌细胞对DNA损伤的反应。为了确定HOXA 5是否在乳腺细胞的生长和稳态中发挥作用，我们研究了它与孕酮受体的相互作用。孕酮受体（PR）属于核受体超家族，其成员响应于与其同源配体的结合而协调乳腺的形态发生。在MCF-7细胞中观察到内源性PR基因的表达增加，随后诱导外源性转染的HOXA 5基因的表达。HOXA 5（而不是HOXB 4、-B5或-B7）激活了两种乳腺癌细胞系（MCF-7和Hs 578 T）中的PR启动子。启动子的缺失和突变分析确定了HOXA 5反式激活PR基因所需的单个HOXA 5结合位点。HOXA 5直接与PR启动子中的该位点结合。因此，HOXA 5可能作为多个靶基因的转录调节因子，其中两个是p53和孕酮受体。
The majority of breast carcinomas show reduced or no expression of the transcription factor, HOXA5. Recently, we have shown that HOXA5 is a potent transactivator of p53 in breast cells and thus may affect the response of breast cancer cells to DNA damage. To determine whether HOXA5 played a role in growth and homeostasis in breast cells, we studied its interaction with the progesterone receptor. The progesterone receptor (PR) belongs to the superfamily of nuclear receptors whose members co-ordinate morphogenesis of the mammary gland in response to binding to their cognate ligands. An increased expression of the endogenous PR gene was seen in MCF-7 cells following induced expression of an exogenously transfected HOXA5 gene. HOXA5, but not HOXB4, -B5, or -B7 activated the PR promoter in two breast cancer cell lines, MCF-7 and Hs578T. Deletion and mutation analysis of the promoter identified a single HOXA5-binding site required for transactivation of the PR gene by HOXA5. HOXA5 binds directly to this site in the PR promoter. Thus, HOXA5 may behave as a transcriptional regulator of multiple target genes, two among which are p53 and the progesterone receptor.