Localization of O-6-alkylguanine transferase in cancer susceptible cells of human female breast

The cell type specific distribution of O-6-alkylguanine-DNA-alkyltransferase (AGT) protein was assessed using immunohistochemical localization in human female breast tissue sections and biochemical quantitation of fractionated cell extracts. The results demonstrated that the AGT protein is predominantly localized in luminal epithelial and myoepithelial cells of the intralobular mammary ducts. Western blot analysis revealed that the AGT level in epithelial cell rich organoid fraction was substantially higher than the whole tissue and fibro-collagenous stromal cell fraction of the normal breast. The quantitative activity measurements confirmed the occurrence of a statistically significant 2.7-fold (P = 0.05) and 4.0-fold (P = 0.04) enriched AGT activity in extracts prepared from the organoids compared to the whole tissue homogenate and fractionated stromal cells, respectively. The results suggest that the invariably high AGT level in malignant compared to the normal breast tissue could be due to AGT accumulation in luminal epithelial and myoepithelial cell mass, increasing as a consequence of the uncontrolled proliferation and differentiation of ductal cells in invasive carcinoma.