Runx2 controls a feed-forward loop between androgen and prolactin-induced protein (PIP) in stimulating T47D cell proliferation.
Runx2 controls a feed-forward loop between androgen and prolactin-induced protein (PIP) in stimulating T47D cell proliferation.
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DOI：
10.1002/jcp.22966
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发表时间：
2012-05
影响因子：
5.6
通讯作者：
Frenkel, Baruch
中科院分区：
文献类型：
--
作者：
Baniwal, Sanjeev K.;Little, Gillian H.;Chimge, Nyam-Osor;Frenkel, Baruch
PIP是由乳腺癌和前列腺癌（BCa、PCa）细胞表达的小多肽。然而，PIP表达的调节及其在癌细胞中的功能都知之甚少。使用乳腺癌和前列腺癌细胞，我们发现Runx2是一种促转移转录因子，在功能上与雄激素受体（AR）相互作用以调节PIP表达。Runx2在C4 - 2B细胞中的表达与AR协同促进PIP表达，而其在T47 D BCa细胞中的敲除废除了基础以及激素刺激的PIP表达。染色质免疫沉淀（ChIP）分析表明Runx2和AR共同占据了PIP开放阅读框上游约11 kb的增强子元件，并且Runx2促进AR募集到增强子。T47D细胞中的PIP敲低损害了DHT刺激的多种AR靶基因的表达，包括PSA、FKBP5、FkB和SGK1。由于PIP的损失，AR活性的抑制至少部分归因于其核转位的废除。PIP敲低还抑制由血清生长因子或双氢睾酮（DHT）驱动的T47 D细胞增殖。我们的数据表明Runx2控制雄激素信号传导和PIP之间的正反馈回路，并且PIP的药理学抑制可能对治疗PIP阳性肿瘤有用。
PIP is a small polypeptide expressed by breast and prostate cancer (BCa, PCa) cells. However, both the regulation of PIP expression and its function in cancer cells are poorly understood. Using breast and prostate cancer cells, we found that Runx2, a pro-metastatic transcription factor, functionally interacts with the Androgen Receptor (AR) to regulate PIP expression. Runx2 expression in C4-2B cells synergized with AR to promote PIP expression, whereas its knockdown in T47D BCa cells abrogated basal as well as hormone stimulated PIP expression. Chromatin immunoprecipitation (ChIP) assays showed that Runx2 and AR co-occupied an enhancer element located ~11kb upstream of the PIP open reading frame, and that Runx2 facilitated AR recruitment to the enhancer. PIP knockdown in T47D cells compromised DHT-stimulated expression of multiple AR target genes including PSA, FKBP5, FASN, and SGK1. The inhibition of AR activity due to loss of PIP was attributable at least in part to abrogation of its nuclear translocation. PIP knockdown also suppressed T47D cell proliferation driven by either serum growth factors or dihydrotestosterone (DHT). Our data suggest that Runx2 controls a positive feedback loop between androgen signaling and PIP, and pharmacological inhibition of PIP may be useful to treat PIP positive tumors.
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影响因子：
3.8
作者：
Gonzalez LO;Corte MD;Vazquez J;Junquera S;Sanchez R;Alvarez AC;Rodriguez JC;Lamelas ML;Vizoso FJ
通讯作者：
Vizoso FJ
DOI：
10.1073/pnas.0409121102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Javed, A;Barnes, GL;Stein, GS
通讯作者：
Stein, GS
影响因子：
2.3
作者：
Blyth, Karen;Vaillant, Francois;Cameron, Ewan R.
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Cameron, Ewan R.
影响因子：
8
作者：
Akech, J.;Wixted, J. J.;Bedard, K.;van der Deen, M.;Hussain, S.;Guise, T. A.;van Wijnen, A. J.;Stein, J. L.;Languino, L. R.;Altieri, D. C.;Pratap, J.;Keller, E.;Stein, G. S.;Lian, J. B.
通讯作者：
Lian, J. B.
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G