Yonsei Med J.  2005 Oct;46(5):597-613. 10.3349/ymj.2005.46.5.597.

Aberrant Cell Cycle Regulation in Cervical Carcinoma

• Kim YT
• Zhao M

• KMID: 2158138
• DOI: http://doi.org/10.3349/ymj.2005.46.5.597

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 p16INK4A-cyclin D1-CDK4/6-pRb-E2F, p21WAF1-p27KIP1-cyclinE-CDK2, and p14ARF-MDM2-p53 pathways. The results from several studies showed aberrant regulation of several cell cycle proteins, such as cyclin D, cyclin E, p16 INK4A, p21WAF1, and p27KIP1, 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.

Keyword

Cell cycle; cervical carcinoma; cyclin

MeSH Terms

Uterine Cervical Neoplasms/*pathology
Tumor Suppressor Protein p53/physiology
Tumor Suppressor Protein p14ARF/physiology
Retinoblastoma Protein/physiology
Proto-Oncogene Proteins c-mdm2/physiology
Humans
Female
E2F Transcription Factors/physiology
Cyclin-Dependent Kinase Inhibitor p27/physiology
Cyclin-Dependent Kinase Inhibitor p21/physiology
Cyclin-Dependent Kinase Inhibitor p16/physiology
Cyclin-Dependent Kinase 4/physiology
Cyclin-Dependent Kinase 2/physiology
Cyclin E/physiology
Cyclin D1/physiology
Cell Cycle/*physiology

Figure

• 

  Fig. 1 Schematic presentation of the HPV viral oncoproteins E6/E7 and cell-cycle regulatory proteins in cervical carcinogenesis.

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