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Biochem Biophys Res Commun. 2015 Jan 9;456(2):580-5. doi: 10.1016/j.bbrc.2014.11.107. Epub 2014 Dec 4.

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

Author information

1
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
2
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. Electronic address: y-watanabe@md.tsukuba.ac.jp.
3
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. Electronic address: mit-kato@md.tsukuba.ac.jp.

Abstract

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.

KEYWORDS:

EGF; ELK-1; Smad; TGF-β; TMEPAI

PMID:
25482449
DOI:
10.1016/j.bbrc.2014.11.107
[Indexed for MEDLINE]

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