[Human papillomaviruses, cell cycle and cervical cancer].
Human papillomaviruses (HPVs) are associated with a broad spectrum of cutaneous and mucosal lesions. Until now, more than 120 genotypes have been identified. Most HPVs are associated with benign lesions. Nevertheless certain HPV types are frequently found in carcinomas. For instance, HPV 16 and 18 which are frequently associated with cervical cancer, are capable of immortalizing and transforming primary keratinocytes. The mechanism of transformation is linked to the viral genome integration into the cell's DNA, accompanied by an overexpression of the E6 and E7 genes. The viral gene products interact with cellular proteins that regulate the cycle progression. In particular, the E6 protein binds to the p53 and the E7 protein binds to the p105(Rb). The inactivation of both cellular proteins distorts the cell cycle and results in genetic instability and cellular gene alterations. This article reviews the role of the viruses in the carcinogenesis, the genome structure and the gene expression of HPVs. It also addresses the cell cycle regulation with a focus on the role of HPVs in cell transformation.
Mougin
C
C
Laboratoire de Virologie - Biologie Cellulaire, EA 2085, Institut d'Etude et de Transfert de Gènes, Faculté de Médecine, Place Saint-Jacques, 25000 Besançon, France.
Humbey
O
O
Gay
C
C
Riethmuller
D
D
D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003043:Cocarcinogenesis; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016679:Genome, Viral; D006801:Humans; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D016160:Retinoblastoma Protein / Q000235:genetics; D012703:Serotyping; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014412:Tumor Virus Infections / Q000150:complications* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics; D014765:Viral Vaccines; D016662:Virus Integration / Q000235:genetics
D004279:DNA, Viral; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D014765:Viral Vaccines