Effect of human papillomavirus type 16 E6 and E7 oncogenes on the activity of the transforming growth factor-?2 (TGF-?2) promoter

Abstract

The effect of the human papillomavirus type 16 (HPV 16) E6 and E7 proteins was studied on the transcriptional activity of the human transforming growth factor beta2 (TGF-beta) promoter in different cell lines. Luciferase tests were performed after co-transfection of cells with TGF-beta2 reporter constructs and HPV 16 E6 or E7 expression vectors. HPV 16 E7, but not E6 significantly repressed TGF-beta2 promoter activity in NIH/3T3 cells, which have wild-type p53 and pRb proteins. The repressive effect of HPV 16 E7 on the transcriptional activity of the TGF-beta2 promoter could be localized to the promoter region -528 to -251 relative to the transcriptional start site. Ability of E7 to bind pRb was necessary to inhibit the TGF-beta2 promoter. Over-expression of the transcription factor E2F-1 had an effect on the TGF-beta2 promoter similar to that of E7, which may indicate that HPV 16 E7 represses the TGF-beta2 promoter by releasing E2F from pRb.

Transcriptional regulation of genes involved in keratinocyte differentiation by human papillomavirus 16 oncoproteins

“…The pAP-1-Luc and pC/EBP-Luc plasmids containing several copies of binding sites for AP-1 and C/EBP transcription factors, respectively, were from Agilent Technologies. The pcDNA-based constructs expressing HPV16 E6 or E7 were described previously [ 24 ].…”

The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

“…E7, with some participation by E6, can inhibit TGFβ signaling in cells containing HPV 20,83,84,88,99,102–104 . On the other hand, E6 and E7 are each reported to increase TGFβ1 promoter activity in cervical cancer cell lines 105 .…”

“…Resistance to TGFβ growth arrest appears to be primarily mediated through E7 88,102 . E7 alone can inhibit growth suppression in non-malignant cells by blocking TGFβ expression and signaling 103,104 . Consequently, TGFβ treatment of HPV- containing cells can stimulate rather than arrest growth 88,102,114 .…”

“…Although whether regulation of TGFβ is important for the loss of LCs in HPV-containing lesions is not yet clear, E7 causes reduced production of TGFβ from infected cells 20,83,84,88,99,102–104 . HPV also inhibits GM-CSF production, preventing LC infiltration into the epithelium 293,294,321 .…”

Molecular Bases of Human Papillomavirus Pathogenesis in the Development of Cervical Cancer

“…Finally, E7 has evolved to escape the immune-response by interfering with cytokines signaling pathways: abrogates the immune surveillance by binding to IRF-1 and preventing activation of the INF and promoters (Barnard & McMillan, 1999;Park et al, 2000), as well as represses the TGF-2 promoter by releasing E2F from pRb (Lee et al, 2002b;Murvai et al, 2004). The cytotoxic response against HPV is also evaded by E7 through the downregulation of TAP1, a key protein for peptide transportation from cytosol into the ER, reducing MHC I-dependent antigen presentation, impairing in this way a specific CTL response (Vambutas et al, 2001).…”