c-Myb down-regulation is associated with human colon cell differentiation, apoptosis, and decreased Bcl-2 expression.
c-myb is expressed in human and murine colonic mucosa and elevated expression occurs in premalignant adenomatous polyps and carcinomas. c-Myb is required for colon cell proliferation, and there is evidence of c-myb down-regulation during differentiation. Recently, c-myb has been implicated in hematopoietic cell survival via regulation of bcl-2 gene expression. However, c-myb expression during terminal differentiation and apoptosis in the colonic crypt has not been examined. The experiments in this study examine the spatial and temporal expression of c-Myb protein in vivo using human colonic crypt sections and in vitro in human colon tumor cell lines undergoing butyrate-induced differentiation and apoptosis. Electron microscopy, together with molecular and biochemical analysis, was used to define the differentiation status of the cells. Results demonstrate a decrease in c-Myb expression during the commitment of cells to differentiation and apoptosis. Decreased levels of c-Myb are accompanied by a decrease in Bcl-2. These data suggest that the transcription factor c-Myb has a role in regulating the balance between proliferation, differentiation, and apoptosis in the colonic crypt. Furthermore, elevated c-Myb levels in colon tumor cells may lead to persistent bcl-2 expression, thus protecting tumor cells from programmed cell death.
Thompson
M A
MA
Ludwig Institute for Cancer Research, P. O. Royal Melbourne Hospital, Victoria, Australia.
Rosenthal
M A
MA
Ellis
S L
SL
Friend
A J
AJ
Zorbas
M I
MI
Whitehead
R H
RH
Ramsay
R G
RG
D000469:Alkaline Phosphatase / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics*; D003106:Colon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D053938:DNA Fragmentation; D015536:Down-Regulation; D004790:Enzyme Induction; D005784:Gene Amplification; D019254:Genes, bcl-2; D006801:Humans; D009857:Oncogenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002087:Butyrates; D019253:Proto-Oncogene Proteins c-bcl-2; D000469:Alkaline Phosphatase