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Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer

BACKGROUND: Cervical carcinogenesis is a multistep process initiated by "high risk" human papillomaviruses (HR-HPV), most commonly HPV16. The infection per se is, however, not sufficient to induce malignant conversion. Transforming Growth Factor β (TGF-β) inhibits epithelial proliferation...

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Autores principales: Diaz-Chavez, Jose, Hernandez-Pando, Rogelio, Lambert, Paul F, Gariglio, Patricio
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248208/
https://www.ncbi.nlm.nih.gov/pubmed/18184435
http://dx.doi.org/10.1186/1476-4598-7-3
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author Diaz-Chavez, Jose
Hernandez-Pando, Rogelio
Lambert, Paul F
Gariglio, Patricio
author_facet Diaz-Chavez, Jose
Hernandez-Pando, Rogelio
Lambert, Paul F
Gariglio, Patricio
author_sort Diaz-Chavez, Jose
collection PubMed
description BACKGROUND: Cervical carcinogenesis is a multistep process initiated by "high risk" human papillomaviruses (HR-HPV), most commonly HPV16. The infection per se is, however, not sufficient to induce malignant conversion. Transforming Growth Factor β (TGF-β) inhibits epithelial proliferation and altered expression of TGF-β or its receptors may be important in carcinogenesis. One cofactor candidate to initiate neoplasia in cervical cancer is the prolonged exposure to sex hormones. Interestingly, previous studies demonstrated that estrogens suppress TGF-β induced gene expression. To examine the expression of TGF-β2, TGF-βRII, p15 and c-myc we used in situ RT-PCR, real-time PCR and immunohistochemistry in transgenic mice expressing the oncogene E7 of HPV16 under control of the human Keratin-14 promoter (K14-E7 transgenic mice) and nontransgenic control mice treated for 6 months with slow release pellets of 17β-estradiol. RESULTS: Estrogen-induced carcinogenesis was accompanied by an increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-E7 mice. TGF-β2 mRNA and protein levels increased in K14-E7 transgenic mice as compared with nontransgenic mice and further increased after hormone-treatment in both nontransgenic and transgenic mice. In contrast, TGF-βRII mRNA and protein levels were decreased in K14-E7 transgenic mice compared to nontransgenic mice and these levels were further decreased after hormone treatment in transgenic mice. We also observed that c-myc mRNA levels were high in K14-E7 mice irrespective of estrogen treatment and were increased in estrogen-treated nontransgenic mice. Finally we found that p15 mRNA levels were not increased in K14-E7 mice. CONCLUSION: These results suggest that the synergy between estrogen and E7 in inducing cervical cancer may in part reflect the ability of both factors to modulate TGF-β signal transduction.
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spelling pubmed-22482082008-02-20 Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer Diaz-Chavez, Jose Hernandez-Pando, Rogelio Lambert, Paul F Gariglio, Patricio Mol Cancer Research BACKGROUND: Cervical carcinogenesis is a multistep process initiated by "high risk" human papillomaviruses (HR-HPV), most commonly HPV16. The infection per se is, however, not sufficient to induce malignant conversion. Transforming Growth Factor β (TGF-β) inhibits epithelial proliferation and altered expression of TGF-β or its receptors may be important in carcinogenesis. One cofactor candidate to initiate neoplasia in cervical cancer is the prolonged exposure to sex hormones. Interestingly, previous studies demonstrated that estrogens suppress TGF-β induced gene expression. To examine the expression of TGF-β2, TGF-βRII, p15 and c-myc we used in situ RT-PCR, real-time PCR and immunohistochemistry in transgenic mice expressing the oncogene E7 of HPV16 under control of the human Keratin-14 promoter (K14-E7 transgenic mice) and nontransgenic control mice treated for 6 months with slow release pellets of 17β-estradiol. RESULTS: Estrogen-induced carcinogenesis was accompanied by an increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-E7 mice. TGF-β2 mRNA and protein levels increased in K14-E7 transgenic mice as compared with nontransgenic mice and further increased after hormone-treatment in both nontransgenic and transgenic mice. In contrast, TGF-βRII mRNA and protein levels were decreased in K14-E7 transgenic mice compared to nontransgenic mice and these levels were further decreased after hormone treatment in transgenic mice. We also observed that c-myc mRNA levels were high in K14-E7 mice irrespective of estrogen treatment and were increased in estrogen-treated nontransgenic mice. Finally we found that p15 mRNA levels were not increased in K14-E7 mice. CONCLUSION: These results suggest that the synergy between estrogen and E7 in inducing cervical cancer may in part reflect the ability of both factors to modulate TGF-β signal transduction. BioMed Central 2008-01-09 /pmc/articles/PMC2248208/ /pubmed/18184435 http://dx.doi.org/10.1186/1476-4598-7-3 Text en Copyright © 2008 Diaz-Chavez et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Diaz-Chavez, Jose
Hernandez-Pando, Rogelio
Lambert, Paul F
Gariglio, Patricio
Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer
title Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer
title_full Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer
title_fullStr Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer
title_full_unstemmed Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer
title_short Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer
title_sort down-regulation of transforming growth factor-β type ii receptor (tgf-βrii) protein and mrna expression in cervical cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248208/
https://www.ncbi.nlm.nih.gov/pubmed/18184435
http://dx.doi.org/10.1186/1476-4598-7-3
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