Journal Article

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

James F. Crish, Frederic Bone, Sivaprakasam Balasubramanian, Tarif M. Zaim, Thomas Wagner, Jeung Yun, Ellen A. Rorke and Richard L. Eckert

in Carcinogenesis

Volume 21, issue 5, pages 1031-1037
Published in print May 2000 | ISSN: 0143-3334
Published online May 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.5.1031
Suprabasal expression of the human papillomavirus type 16 oncoproteins in mouse epidermis alters expression of cell cycle regulatory proteins

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Human papillomavirus (HPV) survives by reactivating DNA replication in post-mitotic cells. In the present study, we describe a mouse model of HPV-dependent disease. 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.

Keywords: BrdU, 5-bromo-2′-deoxyuridine; HPVs, human papillomaviruses.

Journal Article.  5802 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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