title: Cooperative induction of transmembrane prostate androgen induced protein TMEPAI/PMEPA1 by transforming growth factor-β and epidermal growth factor signaling.
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.
authors.affiliation: 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.
authors.forename: Shun
authors.initials: S
authors.lastname: Azami
authors.affiliation: 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.
authors.forename: Thanh Thao
authors.initials: TT
authors.lastname: Vo Nguyen
authors.affiliation: 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.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: 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.
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Kato
mesh_terms: D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D020218:Response Elements; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
chemical_list: C494112:ELK1 protein, human; D008565:Membrane Proteins; C412868:PMEPA1 protein, human; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D050807:ets-Domain Protein Elk-1; D004815:Epidermal Growth Factor
keywords: EGF; ELK-1; Smad; TGF-β; TMEPAI