To test our hypothesis, prostate cancer samples (170) and benign prostatic hyperplasia samples (69) were examined by methylation-specific PCR for three genes: adenomatous polyposis coli (APC), glutathione S-transferase pi (GSTP1), and multidrug resistance 1 (MDR1).
Differential expression of the multidrug resistance 1 (MDR1) protein in prostate cancer cells is independent from anticancer drug treatment and Y box binding protein 1 (YB-1) activity.
Several combination therapies and small P-glycoprotein inhibitors have been proposed to improve the therapeutic potential of docetaxel in prostate cancer.
Receiver operator characteristic curve analyses suggested that CpG island hypermethylation changes at GSTP1, APC, RASSF1a, PTGS2, and MDR1 in various combinations can distinguish primary prostate cancer from benign prostate tissues with sensitivities of 97.3-100% and specificities of 92-100%.
In this study we have investigated the contribution of the P-glycoprotein-mediated drug efflux (multidrug-resistance; MDR) to the cellular resistance of prostate carcinoma-derived cell lines to diverse cytotoxic drugs by detection of P-glycoprotein (P-gp) measurement of P-gp-mediated drug transport and reversal of MDR by chemosensitizers.
Previously, we described that MDR phenotype in PCa could be related with high basal and drug-induced expression of MDR proteins P-Glycoprotein (P-Gp), MRP1, and LRP.
These results provide the first mechanistic link between expression of MRP1 and mutation of p53 in human prostate cancer and support recent clinical associations.
Previously, we described that MDR phenotype in PCa could be related with high basal and drug-induced expression of MDR proteins P-Glycoprotein (P-Gp), MRP1, and LRP.
These data suggest that drug resistance in human prostate cancer may be multifactorial, with MRP and LRP frequently expressed in prostate cancer cells before antineoplastic drug treatment and P-gp expression occasionally acquired after drug exposure.
In addition, we found deregulation of ABCB1, ABCB6, ABCC3, and ABCC10 in recurrent PCa samples and validated differential expression of ABCB6, ABCC3, and ABCC10 in recurrent PCa compared to non-recurrent PCa.
Since ABCC10 gene transcription in human prostate cancer CWR22Rv1 cells was found dependent on E2F binding sequence motif, ABCC10 expression in G<sub>1</sub> and S phases of the cell cycle of CWR22Rv1 cells, was analyzed.
QRT-PCR results demonstrated the elevated expression of ABCA5, ABCB1, ABCB6, ABCC1, and ABCC2 as well as reduced expression of ABCC3 in PCa samples compared to normal prostate tissues.
QRT-PCR results demonstrated the elevated expression of ABCA5, ABCB1, ABCB6, ABCC1, and ABCC2 as well as reduced expression of ABCC3 in PCa samples compared to normal prostate tissues.
Expression of eight ABC transporter genes (ABCA8, ABCB1, ABCC6, ABCC9, ABCC10, ABCD2, ABCG2, and ABCG4) was significantly down-regulated in PCa as compared to NPT, and only two genes (ABCC4 and ABCG1) were up-regulated.
Our results showed that modulation of MRP4 could be a mediator of ZEB1-related resistance to docetaxel in prostate cancer, making it a possible marker for chemotherapy response in patients who do not express MDR1.