Demonstration of MDR1 P-glycoprotein isoform expression in benign and malignant human prostate cells by isoform-specific monoclonal antibodies

Prostate cancers are resistant to many anticancer agents at the time of pre sentation. P-glycoprotein (P-gp) is believed to mediate multidrug resistanc e phenotype. To elucidate the possible role of P-gp in such an intrinsic dr ug resistance of prostate cancers, its expression was examined immunohisoch emically using two P-gp isoform-specific monoclonal antibodies (mAbs) with the paraffin embedded prostate samples derived from five nonmalignant and 3 0 untreated prostate cancer patients. In all of five normal prostate tissue s, P-gp was consistently detected with both mAbs in the epithelial cells, e specially at their apical site, and the level of expression was higher in t he inner zone than in outer zone. On the other hand, tumor cells expressed P-gp heterogeneously in distribution and intensity; in 25 of 30 malignant c ases P-gp expression was clearly demonstrated, whereas its expression was o nly faintly detected in other cases. However, the staining intensities for P-gp in prostate cancer cells were generally lower than in normal prostate epithelial cells. Thus, not only normal prostate epithelial cells but prost ate cancer cells express at least MDR1 P-gp isoform, These results suggest that P-gp expression might play some role in intrinsic drug resistance of p rostate cancer cells to many cytotoxic drugs as well as in relative resista nce of the inner zone cells to the prostate carcinogenesis. (C) 2000 Elsevi er Science Ireland Ltd. All rights reserved.