HPV16 Down-Regulates the Insulin-Like Growth Factor Binding Protein 2 to Promote Epithelial Invasion in Organotypic Cultures


The human papillomaviruses (HPV) are the etiological agents of cervical cancer and the disease progresses through the pre-malignant phases of cervical intraepithelial neoplasia I, II and III (CINI-III), before becoming an invasive carcinoma. Therefore identifying factors, which regulate the transition through the premalignant phases and onto invasive cancer would be of importance clinically, to identify patients at risk of progressing from CIN I to CIN III. We show that expression of E6 and E7 proteins from the high risk HPV16, causes reduced expression of the IGF binding protein 2 (IGFBP2) and this correlates with progression from CIN I to CIN III. By modulating IGFBP2 levels in epithelial cells, we have demonstrated that reduction of IGFBP2 levels is a driving event in epithelial invasion. We have gone on to show that de-regulation of expression of IGFBP2 is due to histone deacetylation of the promoter, which can be reversed by histone deacetylase inhibitors.


Vyšlo v časopise: HPV16 Down-Regulates the Insulin-Like Growth Factor Binding Protein 2 to Promote Epithelial Invasion in Organotypic Cultures. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004988
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004988

Souhrn

The human papillomaviruses (HPV) are the etiological agents of cervical cancer and the disease progresses through the pre-malignant phases of cervical intraepithelial neoplasia I, II and III (CINI-III), before becoming an invasive carcinoma. Therefore identifying factors, which regulate the transition through the premalignant phases and onto invasive cancer would be of importance clinically, to identify patients at risk of progressing from CIN I to CIN III. We show that expression of E6 and E7 proteins from the high risk HPV16, causes reduced expression of the IGF binding protein 2 (IGFBP2) and this correlates with progression from CIN I to CIN III. By modulating IGFBP2 levels in epithelial cells, we have demonstrated that reduction of IGFBP2 levels is a driving event in epithelial invasion. We have gone on to show that de-regulation of expression of IGFBP2 is due to histone deacetylation of the promoter, which can be reversed by histone deacetylase inhibitors.


Zdroje

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