Open AccessTMEPAI / PMEPA 1 enhances tumorigenic activities in lung cancer cells
Author(s) -
Vo Nguyen Thanh Thao,
Watanabe Yukihide,
Shiba Aya,
Noguchi Masayuki,
Itoh Susumu,
Kato Mitsuyasu
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12355
Subject(s) - cancer research , smad , signal transduction , carcinogenesis , cell growth , autocrine signalling , gene knockdown , cancer , cancer cell , chemistry , biology , cell culture , microbiology and biotechnology , medicine , biochemistry , genetics
TMEPAI / PMEPA 1 is a transmembrane protein that was originally identified as a prostatic RNA , the synthesis of which is induced by testosterone or its derivatives. We have recently identified TMEPAI as a direct target gene of transforming growth factor‐β ( TGF ‐β)/Smad signaling that participates in negative feedback control of the duration and intensity of TGF ‐β/Smad signaling. TMEPAI is constitutively and highly expressed in many types of cancer and is associated with poor prognosis. Here, we report that TMEPAI is highly expressed in the lung adenocarcinoma cell lines Calu3, NCI ‐H23, and RERF ‐ LC ‐ KJ . Expression of TMEPAI in these cancer cells was significantly suppressed by a TGF ‐β receptor kinase antagonist, SB 208, and by TGF ‐β neutralizing antibodies. These results suggest that constitutive expression of TMEPAI in these cancer cells depends on autocrine TGF ‐β stimulation. Knockdown of TMEPAI in Calu3 and NCI ‐H23 cells enhanced levels of Smad2 phosphorylation and significantly suppressed cell proliferation in the presence of TGF ‐β, indicating that highly expressed TMEPAI suppresses levels of Smad phosphorylation in these cancer cells and reduces the growth inhibitory effects of TGF ‐β/Smad signaling. Furthermore, knockdown of TMEPAI in Calu3 and NCI ‐H23 cells suppressed sphere formation in vitro and tumor formation in s.c. tissues and in lungs after tail vein injection in NOD ‐ SCID mice in vivo . Together, these experiments indicate that TMEPAI promotes tumorigenic activities in lung cancer cells.