title: Cell cycle aberrations in the pathogenesis of squamous cell carcinoma of the uterine cervix.
abstract: Cancer cells are characterized by limitless proliferative autonomy and immunity to inhibitory and apoptotic signals, thus ensuring growth and metastasis [1]. Epidemiological studies have long implicated human papillomavirus (HPV) as a pathogenic agent in cervical cancer. Progress in cancer research now provides an understanding of how these characteristics are achieved by the interaction of HPV proteins with the cell cycle machinery. Expression of oncoproteins E7 and E6 induces immortalization of cells through their inhibitory effects on tumor suppressor proteins pRb and p53, respectively. Undermining of pRb's growth-inhibitory role with release of E2F transcription factors renders the cells independent of mitogenic stimuli. The abundance of growth transcription factors grants limitless proliferative potential by allowing expression of products such as cyclins A, E, and B, dihydrofolate reductase, and DNA polymerase which fuel the various stages of the cell cycle. There is subsequent disruption of both the G1-S and G2-M cell cycle checkpoints. Overexpression of cyclin E results in chromosomal instability and possible unmasking of genetic mutations, allowing disease progression. Cyclin A grants anchorage-independent growth, facilitating tissue invasion and tumor spread. Apoptotic and growth-inhibitory mechanisms are also evaded. p53 is degraded by E6 and its own downstream protein mdm2. Its other downstream protein, p21 is rendered ineffective against cyclin-cyclin-dependent kinase units by E7, as is p27. The understanding of the molecular pathology of disease will provide us with the ability to prognosticate and treat patients more effectively.
authors.affiliation: Department of Anatomical Pathology, Nelson R. Mandela Medical School, Durban, South Africa.
authors.forename: B
authors.initials: B
authors.lastname: Clarke
authors.forename: R
authors.initials: R
authors.lastname: Chetty
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D005260:Female; D006801:Humans; D014594:Uterine Neoplasms / Q000209:etiology* / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins