A novel functional interplay between Progesterone Receptor-B and PTEN, via AKT, modulates autophagy in breast cancer cells.
A novel functional interplay between Progesterone Receptor-B and PTEN, via AKT, modulates autophagy in breast cancer cells.
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DOI：
10.1111/jcmm.12363
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发表时间：
2014-11
影响因子：
5.3
通讯作者：
Andò S
中科院分区：
文献类型：
--
作者：
De Amicis F;Guido C;Santoro M;Lanzino M;Panza S;Avena P;Panno ML;Perrotta I;Aquila S;Andò S
10号染色体上的磷酸酶和张力蛋白同源物（PTEN）的肿瘤抑制活性是密集的研究工作的主题，尽管关于其在乳腺癌中的调节的信息有限。在此，我们报告，在乳腺癌细胞中，孕酮（OHPg），通过其同源受体PR-B，积极调节PTEN的表达诱导其mRNA和蛋白质水平，并增加PTEN启动子活性。PTEN基因活性的OHPg依赖性上调需要PR-B与PTEN基因启动子内富含Sp1的区域结合。事实上，ChIP和EMSA分析表明，OHPg处理诱导PR和Sp1与转录辅激活因子如SRC 1和CBP一起占据PTEN启动子。PR-B同种型敲除消除了复合物的形成，表明其特异性参与。OHPg/PR-B依赖的PTEN诱导导致PI 3 K/AKT信号的下调，通过增强UVRAG的表达开启自噬过程并导致细胞存活减少。总之，这些发现突出了OHPg/PR-B和乳腺癌肿瘤抑制通路之间的新功能连接。
The tumour suppressor activity of the phosphatase and tensin homologue on chromosome 10 (PTEN) is subject of intense investigative efforts, although limited information on its regulation in breast cancer is available. Herein, we report that, in breast cancer cells, progesterone (OHPg), through its cognate receptor PR-B, positively modulates PTEN expression by inducing its mRNA and protein levels, and increasing PTEN-promoter activity. The OHPg-dependent up-regulation of PTEN gene activity requires binding of the PR-B to an Sp1-rich region within the PTEN gene promoter. Indeed, ChIP and EMSA analyses showed that OHPg treatment induced the occupancy of PTEN promoter by PR and Sp1 together with transcriptional coactivators such as SRC1 and CBP. PR-B isoform knockdown abolished the complex formation indicating its specific involvement. The OHPg/PR-B dependent induction of PTEN causes the down-regulation of PI3K/AKT signal, switching on the autophagy process through an enhanced expression of UVRAG and leading to a reduced cell survival. Altogether these findings highlight a novel functional connection between OHPg/PR-B and tumour suppressor pathways in breast cancer.
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影响因子：
7.8
作者：
Degtyarev, Michael;De Maziere, Ann;Orr, Christine;Lin, Jie;Lee, Brian B.;Tien, Janet Y.;Prior, Wei W.;van Dijk, Suzanne;Wu, Hong;Gray, Daniel C.;Davis, David P.;Stern, Howard M.;Murray, Lesley J.;Hoeflich, Klaus P.;Klumperman, Judith;Friedman, Lori S.;Lin, Kui
通讯作者：
Lin, Kui
影响因子：
--
作者：
De Amicis, F.;Zupo, S.;Ando, S.
通讯作者：
Ando, S.
影响因子：
5.2
作者：
De Amicis F;Russo A;Avena P;Santoro M;Vivacqua A;Bonofiglio D;Mauro L;Aquila S;Tramontano D;Fuqua SA;Andò S
通讯作者：
Andò S
影响因子：
11.4
作者：
KASTNER, P;KRUST, A;CHAMBON, P
通讯作者：
CHAMBON, P
影响因子：
5.6
作者：
De Amicis, Francesca;Perri, Anna;Ando, Sebastiano
通讯作者：
Ando, Sebastiano