The E6/E7 oncogenes of human papilloma virus and estradiol regulate hedgehog signaling activity in a murine model of cervical cancer.
Exp Cell Res
; 381(2): 311-322, 2019 08 15.
Article
em En
| MEDLINE
| ID: mdl-31125556
ABSTRACT
Human papilloma virus oncogenes and estradiol are major etiologic factors associated with cervical cancer. In order to understand the mechanism by which these two factors promote carcinogenesis, the role of the Hedgehog (Hh) signaling pathway was evaluated during the normal growth of cervical epithelium and in the presence of E6/E7 oncogenes and exogenous estradiol. Hh signaling activity was determined in live animals (i.e., Gli-Luc reporter levels) during the estrous cycle and was found to be higher in the cervical area during the major growth phases, proestrus-estrus, in comparison to the diestrus phase. The same pattern was observed in transgenic mice expressing the E6/E7 oncogenes, though with notably higher levels than in control mice. Adding estradiol also markedly increased Gli activity in the cervix and the skin. In agreement with the correlation between high bioluminescence and tissue growth in different context, cervical cell proliferation was reduced upon Hh signaling inhibition in mice. Treatment with itraconazole, a putative novel Hh inhibitor, at an early stage of cervical carcinogenesis, did not decrease Hh signaling but it did reduce growth. Therefore, Hh signaling likely contributes to cervical carcinogenesis and itraconazole is effective to reduce growth but by a mechanism involving additional signaling pathways.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo do Útero
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Proteínas Oncogênicas Virais
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Estradiol
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Proteínas E7 de Papillomavirus
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Proteínas Hedgehog
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2019
Tipo de documento:
Article