Squamous epithelial hyperplasia and carcinoma in mice transgenic for the human papillomavirus type 16 E7 oncogene.

作者: R Herber , A Liem , H Pitot , P F Lambert

DOI: 10.1128/JVI.70.3.1873-1881.1996

关键词: Papillomavirus E7 ProteinsKeratinTransgeneCellular differentiationCarcinogenesisImmunologyCancer researchBiologyPapillomaviridaeHyperplasiaOncogene

摘要: The human papillomavirus type 16 (HPV-16) genome is commonly present in cervical carcinoma, which a subset of the viral genes, E6 and E7, are expressed. HPV-16 E7 gene products can associated with inactivate tumor suppressor proteins p53 Rb (the retinoblastoma susceptibility product), tissue culture cells, these genes display oncogenic properties. These findings have led to hypothesis that contribute carcinogenesis. This has recently been tested by using transgenic mice as an animal model. together were found induce cancers multiple tissues they expressed, including squamous cell cancer most cervix. We extended studies investigate vivo activities when expressed epithelia mice. Grossly, had phenotypes, wrinkled skin was apparent prior appearance hair on neonates, thickened ears, loss adults. In lines expressing higher levels we observed stunted growth mortality at early age, potentially caused incapacity feed. Histological analysis demonstrated causes epidermal hyperplasia lineages high penetrance. epithelial characterized expansion proliferating compartment keratin 10-positive layer cells hyperkeratosis. Hyperplasia sites animals addition skin, mouth palate, esophagus, forestomach, exocervix. lineages, adult developed tumors late life low arose from sebaceous glands histologically be highly differentiated, locally invasive, aggressive their On basis conclude alter parameters sufficiently potentiate tumorigenesis

参考文章(48)
Vousden Kh, Scholefield J, Wrede D, Crawford L, Tidy J, Crook T, Status of c-myc, p53 and retinoblastoma genes in human papillomavirus positive and negative squamous cell carcinomas of the anus. Oncogene. ,vol. 6, pp. 1251- ,(1991)
P. Hawley-Nelson, K.H. Vousden, N.L. Hubbert, D.R. Lowy, J.T. Schiller, HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. The EMBO Journal. ,vol. 8, pp. 3905- 3910 ,(1989) , 10.1002/J.1460-2075.1989.TB08570.X
J A DiPaolo, N C Popescu, C D Woodworth, J Doniger, V Notario, Induction of human cervical squamous cell carcinoma by sequential transfection with human papillomavirus 16 DNA and viral Harvey ras. Oncogene. ,vol. 4, pp. 395- 399 ,(1989)
R. Schlegel, P. M. Howley, Indira Krishnan-Hewlett, C. Yee, C. C. Baker, Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. American Journal of Pathology. ,vol. 119, pp. 361- 366 ,(1985)
J.M. Huibregtse, M. Scheffner, P.M. Howley, A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. The EMBO Journal. ,vol. 10, pp. 4129- 4135 ,(1991) , 10.1002/J.1460-2075.1991.TB04990.X
G. Matlashewski, J. Schneider, L. Banks, N. Jones, A. Murray, L. Crawford, Human papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells. The EMBO Journal. ,vol. 6, pp. 1741- 1746 ,(1987) , 10.1002/J.1460-2075.1987.TB02426.X
K. Münger, B.A. Werness, N. Dyson, W.C. Phelps, E. Harlow, P.M. Howley, Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. The EMBO Journal. ,vol. 8, pp. 4099- 4105 ,(1989) , 10.1002/J.1460-2075.1989.TB08594.X
Brigid Hogan, Elizabeth Lacy, Frank Costantini, Manipulating the mouse embryo: A laboratory manual ,(1986)
A E Griep, R Herber, S Jeon, J K Lohse, R R Dubielzig, P F Lambert, Tumorigenicity by human papillomavirus type 16 E6 and E7 in transgenic mice correlates with alterations in epithelial cell growth and differentiation. Journal of Virology. ,vol. 67, pp. 1373- 1384 ,(1993) , 10.1128/JVI.67.3.1373-1384.1993