Programmed cell death in colorectal carcinogenesis.
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.
Valentini
A M
AM
Department of Histopathology, IRCCS S. De Bellis, Castellana Grotte, Bari, Italy.
Caruso
M L
ML
Armentano
R
R
Pirrelli
M
M
Rizzi
E
E
Lapenna
F
F
Renna
L
L
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
D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53