title: Early genetic and functional events in the pathogenesis of oral cancer.
abstract: Oral squamous cell carcinoma (SCC) is a major world health problem, but the changes leading to the development of malignancy remain essentially unknown. Early changes are thought to include the loss of tumour suppressor genes on chromosomes 3p, 9p, and 17p. Although what genes are involved on chromosome 3 remains speculative, p16 (9p21) and p53 (17p13) are inactivated in a high proportion of oral dysplastic lesions and carcinomas. SCC-derived cell lines are immortal, have decreased growth requirements in vitro, and show a variable capacity to form tumours in athymic mice. Normal oral keratinocytes and cells from potentially malignant lesions invariably senesce at early culture passage, have strict growth requirements in vitro, and are nontumorigenic in vivo. By contrast to normal oral keratinocytes, cells from potentially malignant lesions are defective in their capacity to terminally differentiate in suspension culture. Loss of cellular senescence and gain of the immortal phenotype is associated with inactivation of p16 and p53.
authors.affiliation: Department of Oral and Dental Science, University of Bristol, United Kingdom.
authors.forename: S S
authors.initials: SS
authors.lastname: Prime
authors.forename: J W
authors.initials: JW
authors.lastname: Eveson
authors.forename: P G
authors.initials: PG
authors.lastname: Guest
authors.forename: E K
authors.initials: EK
authors.lastname: Parkinson
authors.forename: I C
authors.initials: IC
authors.lastname: Paterson
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D016923:Cell Death; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D009061:Mouth Mucosa / Q000166:cytology; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured