Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways

© 2017, Spandidos Publications. All rights reserved. Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types...

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Main Authors: Ariyaphong Wongnoppavich, Nahathai Dukaew, Sirinthip Choonate, Kongthawat Chairatvit
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/56763
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spelling th-cmuir.6653943832-567632018-09-05T03:48:28Z Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways Ariyaphong Wongnoppavich Nahathai Dukaew Sirinthip Choonate Kongthawat Chairatvit Biochemistry, Genetics and Molecular Biology Medicine © 2017, Spandidos Publications. All rights reserved. Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types of malignant cells. Therefore, the regulation of maspin expression may depend on the genetic or epigenetic background and the specific microenvironment of carcinoma cells. In the present study, it was demonstrated that transforming growth factorβ1 (TGF-β1) induced maspin expression at the transcript and protein levels in the human cervical carcinoma HeLa and human oral squamous carcinoma HSC4 cell lines. The inhibition of the mothers against decapentaplegic homolog (Smad)-dependent pathway by a Smad3-specific inhibitor suppressed maspin induction by TGF-β1 in HeLa cells. Inhibition of the non-Smad pathway by pretreatment with the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor U0126, or the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB202190, attenuated the effect of TGF-β1 on maspin upregulation, whereas pretreatment with pyrrolidine dithiocarbamate (a nuclear factorκB inhibitor), wortmannin (a phosphoinositide 3-kinase inhibitor) or SP600125 (a c-Jun N-terminal kinase inhibitor) did not. Notably, none of these inhibitors eliminated the TGF-β1-induced phosphorylation of Smad2. In addition, mutations at p53-binding sites in the maspin promoter suppressed TGF-β1-induced maspin expression, indicating the necessity of intact p53-binding sites on the maspin promoter. In summary, the induction of maspin expression in HeLa cells requires the convergence of TGF-β1-induced Smad and non-Smad signaling pathways, in which the latter acts via the intermediate signaling molecules MEK1/2 and p38 MAPK. 2018-09-05T03:29:58Z 2018-09-05T03:29:58Z 2017-05-01 Journal 17921082 17921074 2-s2.0-85017469736 10.3892/ol.2017.5939 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85017469736&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/56763
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
Medicine
spellingShingle Biochemistry, Genetics and Molecular Biology
Medicine
Ariyaphong Wongnoppavich
Nahathai Dukaew
Sirinthip Choonate
Kongthawat Chairatvit
Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways
description © 2017, Spandidos Publications. All rights reserved. Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types of malignant cells. Therefore, the regulation of maspin expression may depend on the genetic or epigenetic background and the specific microenvironment of carcinoma cells. In the present study, it was demonstrated that transforming growth factorβ1 (TGF-β1) induced maspin expression at the transcript and protein levels in the human cervical carcinoma HeLa and human oral squamous carcinoma HSC4 cell lines. The inhibition of the mothers against decapentaplegic homolog (Smad)-dependent pathway by a Smad3-specific inhibitor suppressed maspin induction by TGF-β1 in HeLa cells. Inhibition of the non-Smad pathway by pretreatment with the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor U0126, or the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB202190, attenuated the effect of TGF-β1 on maspin upregulation, whereas pretreatment with pyrrolidine dithiocarbamate (a nuclear factorκB inhibitor), wortmannin (a phosphoinositide 3-kinase inhibitor) or SP600125 (a c-Jun N-terminal kinase inhibitor) did not. Notably, none of these inhibitors eliminated the TGF-β1-induced phosphorylation of Smad2. In addition, mutations at p53-binding sites in the maspin promoter suppressed TGF-β1-induced maspin expression, indicating the necessity of intact p53-binding sites on the maspin promoter. In summary, the induction of maspin expression in HeLa cells requires the convergence of TGF-β1-induced Smad and non-Smad signaling pathways, in which the latter acts via the intermediate signaling molecules MEK1/2 and p38 MAPK.
format Journal
author Ariyaphong Wongnoppavich
Nahathai Dukaew
Sirinthip Choonate
Kongthawat Chairatvit
author_facet Ariyaphong Wongnoppavich
Nahathai Dukaew
Sirinthip Choonate
Kongthawat Chairatvit
author_sort Ariyaphong Wongnoppavich
title Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways
title_short Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways
title_full Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways
title_fullStr Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways
title_full_unstemmed Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways
title_sort upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of smad and non-smad signaling pathways
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85017469736&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/56763
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