Title: Molecular Signature of HPV-Induced Carcinogenesis: pRb, p53 and Gene Expression Profiling
Volume: 10
Issue: 1
Author(s): Agueda Buitrago-Perez, Guillermo Garaulet, Ana Vazquez-Carballo, Jesus M. Paramio and Ramon Garcia-Escudero
Affiliation:
Keywords:
Human papillomavirus, E6, E7, cervical cancer, oropharyngeal cancer, gene expression profiling, pRb, p53
Abstract: The infection by mucosal human papillomavirus (HPV) is causally associated with tumor development in cervix and oropharynx. The mechanisms responsible for this oncogenic potential are mainly due to the product activities of two early viral oncogenes: E6 and E7. Although a large number of cellular targets have been described for both oncoproteins, the interaction with tumor suppressors p53 and retinoblastoma protein (pRb) emerged as the key functional activities. E6 degrades tumor suppressor p53, thus inhibiting p53-dependent functions, whereas E7 binds and degrades pRb, allowing the transcription of E2F-dependent genes. Since these two tumor suppressors exert their actions through transcriptional modulation, functional genomics has provided a large body of data that reflects the altered gene expression of HPVinfected cells or tissues. Here we will review the similarities and differences of these findings, and we also compare them with those obtained with transgenic mouse models bearing the deletion of some of the viral oncogene targets. The comparative analysis supports molecular evidences about the role of oncogenes E6 and E7 in the interference with the mentioned cellular functions, and also suggests that the mentioned transgenic mice can be used as models for HPV-associated diseases such as human cervical, oropharynx, and skin carcinomas.