1887

Abstract

The close association between human papillomavirus type 16 (HPV-16) and cervical cancer implies some role for the virus in the development of this disease. Recent studies have shown that HPV-16, under the control of strong heterologous promoters, can cooperate with the activated oncogene to transform primary baby rat kidney cells. Virus types associated with benign lesions, e.g. HPV-6 and -11, do not function in this system. The discrimination between virus types associated with benign and tumorigenic lesions by this assay implicate it as a useful system for the study of transformation The studies reported here investigate the activity of the HP V -16 early gene product E2 in transformation. In the presence of exogenous E2, endogenous viral promoters are stimulated sufficiently to give a high efficiency of transformation in primary epithelial cells. This transactivation by E2 obviates the need for heterologous promoters, and implicates increased viral gene expression as a prerequisite for transformation. The stimulatory effect of E2 appears to be mediated through increased levels of expression of the E7 protein, which has been shown in similar assays to be sufficient to give transformation in cooperation with CAT assays confirm that HPV-16 E2 can transactivate the HPV-16 early promoters. These studies demonstrate some of the elements in a complex series of events likely to be involved in the development of cervical carcinomas.

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1990-01-01
2024-10-08
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