Evidence for post-transcriptional down-regulation of the apoptosis-related gene bcl-2 in human colorectal cancer.
This retrospective study was undertaken to investigate the expression of bcl-2 protein and messenger RNA in colorectal cancer (CRC). Immunohistochemical analysis using a monoclonal mouse antibody to the bcl-2 protein and in situ hybridization using a digoxigenin-labelled bcl-2 cRNA probe were carried out on formalin-fixed and paraffin-embedded specimens from 53 colorectal adenocarcinomas, 27 liver secondaries, and 60 adenomas with various degrees of dysplasia. Normal human tonsil sections were used as positive controls. Expression of bcl-2 protein and of messenger RNA was evaluated semiquantitatively. The expression of bcl-2 protein was gradually and significantly lost during the progression from moderately dysplastic adenoma to primary CRC (moderate/severe dysplasia: Mann-Whitney U-test, p=0.0001; severe dysplasia/primary CRC: p=0.027), whereas the cellular expression of bcl-2 mRNA was gradually increased during the dysplasia/adenoma-carcinoma neoplastic sequence. These observations suggest that in a proportion of colorectal cancer cases, the bcl-2 proto-oncogene expression may be down-regulated at a post-transcriptional level.
Berney
C R
CR
Department of Surgery, Prince of Wales Hospital, University of New South Wales, Randwick, NSW 2031, Australia.
Downing
S R
SR
Yang
J L
JL
Russell
P J
PJ
Crowe
P J
PJ
D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D019254:Genes, bcl-2; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*; D012189:Retrospective Studies
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm