Cooperative induction of transmembrane prostate androgen induced protein TMEPAI/PMEPA1 by transforming growth factor-β and epidermal growth factor signaling

被引:19
作者
Azamil, Shun
Thanh Thao Vo Nguyen
Watanabe, Yukihide [1 ]
Kato, Mitsuyasu
机构
[1] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Expt Pathol, Tsukuba, Ibaraki 3058575, Japan
关键词
TMEPAI; EGF; TGF-beta; ELK-1; Smad; TGF-BETA; TUMOR-SUPPRESSOR; FACTOR RECEPTOR; RAS; GENE; TRANSDUCTION; MECHANISMS; EXPRESSION; PATHWAYS; TMEPAI;
D O I
10.1016/j.bbrc.2014.11.107
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
TMEPAI/PMEPA1 (transmembrane prostate androgen induced-RNA/prostate transmembrane protein, androgen induced 1) is a pro-tumorigenic factor induced by TGF-beta signaling and constitutive TMEPAI expression in lung cancer cells depends on activated autocrine TGF-beta signaling. Here we demonstrate a novel mechanism of TMEPAI transcriptional co-regulation by EGF signaling. Interestingly, we found that ELK-1, downstream of EGFR/Ras/MAPK pathway, modulates TMEPAI expression. ELK-1 binds to the first intron (+1037 to +1294) of the TMEPAI gene together with TGF-beta activated Smad3 and enhances the transcription of TMEPAI. Furthermore, TMEPAI gene activation by EGF and TGF-beta signaling was reduced by the MEK inhibitor U0126. Together, EGF signaling collaboratively regulates TGF-beta-induced TMEPAI expression. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:580 / 585
页数:6
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