Immunohistochemical analysis of Bcl-2 and Bax expression in relation to cell turnover and epithelial differentiation markers in the non-lactating human mammary gland epithelium

Abstract

The expression of the apoptosis-related proteins Bcl-2 and Bax was investigated by immunohistochemistry in the normal non-lactating human mammary gland in relation to cell proliferation and apoptosis. In order to characterize individual Bax/Bcl-2-immunoreactive cells, the epithelial markers cytokeratin 14 and 19 and the macrophage marker CD 68 were used. Secretory-like differentiation of epithelial cells was characterized by histochemistry and lectin staining of surface glycoconjugates. Cell proliferation was exclusively found in glandular epithelial cells with broad contact to the ductular lumen, whereas nuclei with apoptosis-related DNA fragmentation were seen predominantly in basally located glandular epithelial cells and in myoepithelial cells. Weak immunoreactivity for Bcl-2 and Bax was present throughout all epithelia, suggesting a balance between pro- and antiapoptotic effects in the majority of epithelial cells. However, specific cells showed a strong staining for Bax or Bcl-2. The strongly Bcl-2-immunoreactive epithelial cells were not identical with proliferating cells, but they resembled them in configuration and in the luminal intraepithelial position. In contrast, the strongly Bax-positive epithelial cells had no or only a narrow contact to the ductular lumen. The different patterns of Bax/Bcl-2 immunoreactivity in specific glandular epithelial cells suggest that there are also different grades of susceptibility towards apoptotic stimuli in individual glandular epithelial cells. We conclude that specific Bax/Bcl-2 expression patterns could reflect particular cell differentiation states, and that the strongly Bcl-2-positive cells in part could represent epithelial stem cells.

Side population purified from hepatocellular carcinoma cells harbors cancer stem cell–like properties

“…It has been reported that ormal stem/precursor cells of various tissue origins express a high level of anti-apoptotic protein such as Bcl-2. 29,30 Taken together, an anti-apoptotic function might be a preferentially prepared mechanism in both normal and cancer stem cells. Next, we examined the tumorigenic potential and self-renewal ability of SP cells in NOD/SCID xenotransplant assay.…”

Isolation of multipotent stem cells from mouse adipose tissue

“…In in vitro cell cultures, stem cells did not maintain the expression of p75NTR. Some cells inherited the selfrenewal capacity character of stem cells while other cells became committed or progenitor cells [32][33][34].…”

Side population in the pancreatic cancer cell lines SW1990 and CFPAC-1 is enriched with cancer stem-like cells

“…This revealed that SP cells are more tolerant to apoptosis than non-SP cells. It has been reported that normal stem/precursor cells of various tissue origins express high levels of anti-apoptotic proteins such as Bcl-2 (22). Moreover, resistance of apoptosis has been suggested as a feature to enrich cancer stem cells from tumor specimens or tumor cell lines (23,24).…”