The association of Id-1, MIF and GSTpi with acquired drug resistance in hormone independent prostate cancer cells.
Most patients with prostate cancer respond to androgen ablation therapy, but the tumor eventually progresses to an androgen-independent stage with multiple anti-cancer drug resistance. Novel therapeutic strategies for hormone independent prostate cancer need to be developed. The genes for Id-1, MIF and GSTpi were up-regulated in drug resistant cells of hormone independent prostate cancer cells using cDNA microarray gene expression analysis. In this study we aimed to investigate whether constitutive overexpression of these candidate genes in cells can affect cellular resistance to chemotherapeutic agents. The mRNA expression was determined by reverse transcriptase-polymerase chain reaction, and the Id-1, MIF and GSTpi protein contents in these cell lines were measured by Western blotting. Susceptibility of the cells to chemotherapeutic agents including doxorubicin, paclitaxel and cyclophosphamide was determined by microculture tetrazolium bromide assay. The analysis of apoptosis was assessed by annexin V assay. The cytotoxity assay results demonstrated that cells overexpressing the Id-1 gene increased in their resistance to doxorubicin, paclitaxel and cyclophosphamide. MIF expression can drive cells to increase in their resistance to paclitaxel, and GSTpi expression confers drug resistance to doxorubicin and cyclophosphamide. The induction of mdr1 gene expression was noted in up-regulation of MIF and GSTpi. Our findings suggest that overproduction of the Id-1, MIF and GSTpi proteins and coinduction of mdr-1 play an important role in the development of acquired drug resistance to various drugs of prostate cancer cells.
Lin
Jau-Chen
JC
Graduate Institute of Life Sciences, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Chang
Sun-Yran
SY
Hsieh
Dar-Shih
DS
Lee
Chi-Feng
CF
Yu
Dah-Shyong
DS
D000818:Animals; D017304:Annexin A5 / Q000235:genetics; D045744:Cell Line, Tumor; D017931:DNA Primers; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs; D051798:Inhibitor of Differentiation Protein 1; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D017304:Annexin A5; D017931:DNA Primers; C497454:ID1 protein, rat; D051798:Inhibitor of Differentiation Protein 1; D008263:Macrophage Migration-Inhibitory Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D005982:Glutathione Transferase