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

• Published in: Biochemical and biophysical research communications Vol. 456; no. 2; pp. 580 - 585
• Main Authors: Azami, Shun, Vo Nguyen, Thanh Thao, Watanabe, Yukihide, Kato, Mitsuyasu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.01.2015
• Subjects: autocrine signaling; Cell Line, Tumor; EGF; ELK-1; epidermal growth factor; Epidermal Growth Factor - metabolism; ets-Domain Protein Elk-1 - metabolism; gene activation; Gene Expression Regulation; Humans; introns; Introns - genetics; lung neoplasms; Membrane Proteins - genetics; mitogen-activated protein kinase; neoplasm cells; Response Elements; Signal Transduction; Smad; Smad3 Protein - metabolism; TGF-β; TMEPAI; transcription (genetics); transforming growth factor beta; Transforming Growth Factor beta - metabolism; transmembrane proteins; TMEPAI; ELK-1; TGF-β; Smad; EGF
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2014.11.107

•EGF and TGF-β signaling cooperatively regulate TMEPAI transcription.•EGF-responsive elements reside in the first intron of TMEPAI gene.•ELK-1 mediates the EGF-induced enhancement of TMEPAI expression. TMEPAI/PMEPA1 (transmembrane prostate androgen induced-RNA/prostate transmembrane protein, androgen induced 1) is a pro-tumorigenic factor induced by TGF-β signaling and constitutive TMEPAI expression in lung cancer cells depends on activated autocrine TGF-β 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-β activated Smad3 and enhances the transcription of TMEPAI. Furthermore, TMEPAI gene activation by EGF and TGF-β signaling was reduced by the MEK inhibitor U0126. Together, EGF signaling collaboratively regulates TGF-β-induced TMEPAI expression.