Suprabasal expression of the human papillomavirus type 16 oncoproteins in mouse epidermis alters expression of cell cycle regulatory proteins

Abstract

In these mice, DNA synthesis is activated in suprabasal keratinocytes, leading to acanthosis, parakeratosis and enhanced desquamation. The full-length E6/E7 transcript and two alternately spliced products are produced and in most lines the predominant product is E6*. In the present study, we examine the effects of E6/E7 on cell cycle regulatory protein expression. E6/E7 expression in mouse epidermis is correlated with increased levels of the p53, p21, p27, cdk2, cdk4, cdk6, cyclin D1 and cyclin E regulatory proteins. Hyperproliferation is also observed in the buccal mucosa and the tongue epithelia of E6/E7 mice, and p53 levels are markedly increased in these epithelia. These results suggest that the major changes in cell cycle regulatory protein expression are in response to the presence of E7 and that E6 has a lesser impact.

Protein Kinase D Is Implicated in the Reversible Commitment to Differentiation in Primary Cultures of Mouse Keratinocytes

“…Under normal steady state conditions, proliferation is strictly restricted to the basal layer, although aberrant suprabasal proliferation is observed during wound healing and in some diseased states when normal epidermal proliferation and differentiation are perturbed (2,3).…”

Papillomavirus Type 16 Oncogenes Downregulate Expression of Interferon-Responsive Genes and Upregulate Proliferation-Associated and NF-κB-Responsive Genes in Cervical Keratinocytes

“…The E6 and E7 viral genes are expressed at low levels in proliferating basal cells, but transcription is activated as cells enter the terminal differentiation pathway (11,16). E6 and E7 delay keratinocyte differentiation, reactivate host DNA synthesis, and stimulate cell cycle progression (60), allowing the virus to utilize host DNA synthetic enzymes to replicate its genome.…”

Translational Regulation of Human Papillomavirus Type 16 E7 mRNA by the Peptide SEQIKA, Shared by Rabbit α1-Globin and Human Cytokeratin 7

“…Also, the long latency (decades) required for cervical cancer development after primary viral infection and the absence of tumor-specific modifications in the viral oncogenes imply the action of additional factors in the outcome of genital cancer. Therefore, evaluation of the factors that affect viral gene expression is fundamental to clarifying the mechanism of cervical carcinogenesis.This laboratory is investigating the factors that regulate the expression of the high-risk HPV type 16 (HPV16) E7 oncoprotein that is believed to play a major role in cervical neoplasia (7,38). The ability of high-risk HPVs to contribute to malignant progression seems to depend on the expression of viral E6 and E7 oncoproteins, known to inactivate two cellular tumor suppressor gene products, p53 and retinoblastoma protein (35).…”

“…This laboratory is investigating the factors that regulate the expression of the high-risk HPV type 16 (HPV16) E7 oncoprotein that is believed to play a major role in cervical neoplasia (7,38). The ability of high-risk HPVs to contribute to malignant progression seems to depend on the expression of viral E6 and E7 oncoproteins, known to inactivate two cellular tumor suppressor gene products, p53 and retinoblastoma protein (35).…”