title: Aberrant cell cycle regulation in cervical carcinoma.
abstract: Carcinoma of the uterine cervix is one of the most common malignancies among women worldwide. Human papillomaviruses (HPV) have been identified as the major etiological factor in cervical carcinogenesis. However, the time lag between HPV infection and the diagnosis of cancer indicates that multiple steps, as well as multiple factors, may be necessary for the development of cervical cancer. The development and progression of cervical carcinoma have been shown to be dependent on various genetic and epigenetic events, especially alterations in the cell cycle checkpoint machinery. In mammalian cells, control of the cell cycle is regulated by the activity of cyclin-dependent kinases (CDKs) and their essential activating coenzymes, the cyclins. Generally, CDKs, cyclins, and CDK inhibitors function within several pathways, including the p16(INK4A)-cyclin D1-CDK4/6-pRb-E2F, p21(WAF1)- p27(KIP1)-cyclinE-CDK2, and p14(ARF)-MDM2-p53 pathways. The results from several studies showed aberrant regulation of several cell cycle proteins, such as cyclin D, cyclin E, p16(INK4A), p21(WAF1), and p27(KIP1), as characteristic features of HPV- infected and HPV E6/E7 oncogene-expressing cervical carcinomas and their precursors. These data suggested further that interactions of viral proteins with host cellular proteins, particularly cell cycle proteins, are involved in the activation or repression of cell cycle progression in cervical carcinogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, Women's Cancer Clinic, Women's life and Science Institute, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. ytkchoi@yumc.yonsei.ac.kr
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D019938:Cyclin D1 / Q000502:physiology; D019927:Cyclin E / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2 / Q000502:physiology; D051358:Cyclin-Dependent Kinase 4 / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology; D050684:E2F Transcription Factors / Q000502:physiology; D005260:Female; D006801:Humans; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D016160:Retinoblastoma Protein / Q000502:physiology; D025803:Tumor Suppressor Protein p14ARF / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: C493956:CDKN1A protein, human; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4