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Recillas, F; Peralta-Zaragoza, O; Bermudez-Morales, V; Gutierrez-Xicotencatl, L; Alcocer-Gonzalez, J; Madrid-Marina, V (2006)

E6 AND E7 ONCOPROTEINS FROM HUMAN PAPILLOMAVIRUS TYPE 16 INDUCE ACTIVATION OF HUMAN TRANSFORMING GROWTH FACTOR SS(1) PROMOTER THROUGHOUT SP1 RECOGNITI

VIRAL IMMUNOL 19(3):468-480
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Human Papillomavirus (HPV) infection is the main etiologic agent of cervical cancer and HPV E6 and E7 oncogenes trans-regulate many cellular genes. An association between TGF-beta(1) gene expression and cervical cancer development has been suggested; however, the mechanisms by which HPV influences TGF-beta(1) expression remain unclear. In the present study we analyzed the mechanism through which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta(1) promoter in cervical tumor cells. Our results showed that E6 and E7 increased TGF-P, promoter activity. Furthermore, we identified a specific DNA sequence motif in the TGF-beta(1) core promoter that is responsible for trans -activation and that corresponds to the Sple-binding site associated with HPV-16 E6 and E7 oncoproteins. Mutational analysis showed that the Sple recognition site abolished the trans-activation caused by E6 and E7. These results suggest a physical interaction and functional cooperation between viral oncoproteins and cellular regulatory elements of the TGF-beta(1) promoter, and may explain the contribution of HPV-16 to TGF-beta(1) gene expression in cervical cancer.