Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response.

ABSTRACT: Integration of high-risk human papillomavirus (HRHPV) into the host genome is a key event in cervical neoplastic progression. Integration is associated with deregulated expression of the viral oncogenes E6 and E7 and acquisition of a selective growth advantage for cells containing integrants. Overexpression of the viral transcriptional regulator E2 from heterologous promoters has an inhibitory effect on transcription from integrated HRHPV. Therefore, we hypothesized that loss of E2-expressing episomes from cells in which integration had previously occurred would be required for such cells to gain a growth advantage. Using the unique W12 model of cervical squamous carcinogenesis, we show that cells containing integrated HPV16 reproducibly emerged during long-term culture when there had been

SUBMITTER: Pett MR 

PROVIDER: S-EPMC1383496 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature