title: Programmed cell death in colorectal carcinogenesis.
abstract: The most studied mechanism of malignant transformation has been cell proliferation. The relationship between programmed cell death (apoptosis), cell proliferation, and apoptosis regulatory genes (p53 and bcl-2), was studied in normal colonic epithelium, 26 sporadic adenomas both early and late, 25 FAP adenomas, and 34 carcinomas. We showed a decrease in programmed cell death and an increase in cell proliferation during the transition from adenoma to carcinoma. The increase of expression of p53 from early (10%) to late adenomas (87%) contrasted with the decrease of bcl-2 staining. Sixty-two per cent and 23% of carcinomas were reactive for p53 and bcl-2 respectively. Abnormal early activation of the bcl-2 gene, rather than late p53 gene mutation appears to be responsible for inhibition of apoptosis in colorectal carcinogenesis. bcl-2 was higher in FAP adenomas than in sporadic cases, and in carcinomas favouring the accumulation of long-living cells, which are more subject to mutation and thus cancerization.
authors.affiliation: Department of Histopathology, IRCCS S. De Bellis, Castellana Grotte, Bari, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Valentini
authors.forename: M L
authors.initials: ML
authors.lastname: Caruso
authors.forename: R
authors.initials: R
authors.lastname: Armentano
authors.forename: M
authors.initials: M
authors.lastname: Pirrelli
authors.forename: E
authors.initials: E
authors.lastname: Rizzi
authors.forename: F
authors.initials: F
authors.lastname: Lapenna
authors.forename: L
authors.initials: L
authors.lastname: Renna
mesh_terms: D017209:Apoptosis; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53