title: E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta1 promoter throughout Sp1 recognition sequence.
abstract: 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-beta1 gene expression and cervical cancer development has been suggested; however, the mechanisms by which HPV influences TGF-beta1 expression remain unclear. In the present study we analyzed the mechanism through which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta1 promoter in cervical tumor cells. Our results showed that E6 and E7 increased TGF-beta1 promoter activity. Furthermore, we identified a specific DNA sequence motif in the TGF-beta1 core promoter that is responsible for trans-activation and that corresponds to the Sp1e-binding site associated with HPV-16 E6 and E7 oncoproteins. Mutational analysis showed that the Sp1e 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-beta1 promoter, and may explain the contribution of HPV-16 to TGF-beta1 gene expression in cervical cancer.
authors.affiliation: Division of Molecular Biology of Pathogens, National Institute of Public Health, Cuernavaca, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Peralta-Zaragoza
authors.forename: Víctor
authors.initials: V
authors.lastname: Bermúdez-Morales
authors.forename: Lourdes
authors.initials: L
authors.lastname: Gutiérrez-Xicotencatl
authors.forename: Juan
authors.initials: J
authors.lastname: Alcocer-González
authors.forename: Félix
authors.initials: F
authors.lastname: Recillas-Targa
authors.forename: Vicente
authors.initials: V
authors.lastname: Madrid-Marina
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C068651:E6 protein, Human papillomavirus type 16; C059731:oncogene protein E7, Human papillomavirus type 16