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TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells
TMEPAI/PMEPA1 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 neg...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317935/ https://www.ncbi.nlm.nih.gov/pubmed/24438557 http://dx.doi.org/10.1111/cas.12355 |
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author | Vo Nguyen, Thanh Thao Watanabe, Yukihide Shiba, Aya Noguchi, Masayuki Itoh, Susumu Kato, Mitsuyasu |
author_facet | Vo Nguyen, Thanh Thao Watanabe, Yukihide Shiba, Aya Noguchi, Masayuki Itoh, Susumu Kato, Mitsuyasu |
author_sort | Vo Nguyen, Thanh Thao |
collection | PubMed |
description | TMEPAI/PMEPA1 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, SB208, 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. |
format | Online Article Text |
id | pubmed-4317935 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43179352015-10-05 TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells Vo Nguyen, Thanh Thao Watanabe, Yukihide Shiba, Aya Noguchi, Masayuki Itoh, Susumu Kato, Mitsuyasu Cancer Sci Original Articles TMEPAI/PMEPA1 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, SB208, 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. BlackWell Publishing Ltd 2014-03 2014-02-18 /pmc/articles/PMC4317935/ /pubmed/24438557 http://dx.doi.org/10.1111/cas.12355 Text en © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Vo Nguyen, Thanh Thao Watanabe, Yukihide Shiba, Aya Noguchi, Masayuki Itoh, Susumu Kato, Mitsuyasu TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells |
title | TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells |
title_full | TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells |
title_fullStr | TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells |
title_full_unstemmed | TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells |
title_short | TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells |
title_sort | tmepai/pmepa1 enhances tumorigenic activities in lung cancer cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317935/ https://www.ncbi.nlm.nih.gov/pubmed/24438557 http://dx.doi.org/10.1111/cas.12355 |
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