Modulation of MDR-1 gene by MIF and GSTpi with drug resistance generation in hormone independent prostate cancer.
The expression of MIF and GSTpi were upregulated in prostate cancer cells with mulitdrug resistant phenotype. The aim of this study is to determine the relationship between these genes and multidrug resistance (mdr-1) gene in acquired multidrug resistance of prostate cancer. The expression of MIF, GSTpi and gp-170 in multidrug resistant (MDR) subline or native cells were determined using flow cytometry and western blotting. The mRNA level of various genes was analyzed with RT-PCR method. The chemosensitivity of tumor cells and stable transfectants to paclitaxel was measured using MTT (tetrazolium bromide) assay. The protein levels of MIF, GSTpi and gp-170 increased in MDR sublines of prostate cancer when compared with their parental cells. The MIF and GSTpi stable transfectants expressed higher MIF and GSTpi protein levels than their parental cells in western blotting analysis, respectively. The expression of mdr-1 gene and the production of pg-170 were also increased in either MIF or GSTpi stable transfectants when compared with vector control by using RT-PCR and flow cytometric analysis. The MTT results demonstrated that the increased chemoresistance was correlated with the increased production of gp-170 protein in either MIF or GSTpi transfectants. The upregulation of MIF and GSTpi during the development of acquired drug resistance of hormone independent prostate cancer may simultaneously and partially modulate the activation of gp-170.
Yu
D-S
DS
Uro-Oncology Laboratory, Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C. yuds@ms21.hinet.net
Lin
J C
JC
Hsieh
D S
DS
Chang
S Y
SY
Lee
C F
CF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival; D005434:Flow Cytometry; D051549:Glutathione S-Transferase pi / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008263:Macrophage Migration-Inhibitory Factors; D051549:Glutathione S-Transferase pi