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.

The gamma delta T lymphocytes of the perinatal murine thymus.

We have previously shown that the adult thymus contains three subsets of gamma delta T cells that can be defined by the expression of THY-1 and heat-stable antigen (HSA). In this study, the number of cells in each of these thymic gamma delta populations was investigated at different stages throughout life. In adult mice, the populations stay relatively constant, however, in contrast, there were major variations in them early in development. It was shown that only two of the gamma delta populations were present in the prenatal thymus, a major population of Thy-1+ HSA - cells, and a smaller population of Thy-1+ HSA+ cells. However, after birth, most of the Thy-1+ HSA - cells appear to loose the Thy-1 antigen, forming the third population of HSA - Thy-1 - cells. The adult configuration of populations appeared to be established within the first week after birth. Therefore, whereas the gamma delta populations stayed relatively constant from this time point onwards, there were major variations early in development. Throughout life, most gamma delta thymocytes are CD4- CD8-, however, in the neonatal thymus, there are some CD+ and CD+ gamma delta thymocytes, and these are contained in the Thy-1+ HSA - population.