Testosterone modulates mitochondrial aconitase in the full-length human androgen receptor-transfected PC-3 prostatic carcinoma cells.
In vitro studies indicated that dihydrotestosterone (DHT) stimulates the enzymatic activity of the mitochondrial aconitase (mACON) in androgen-sensitive prostatic carcinoma cells, LNCaP. Cell proliferation assay determined that DHT doubles the optimal proliferation response of LNCaP cells. The androgen-insensitive human prostatic carcinoma cells, PC-3, were overexpressed in the human androgen receptor to assess the involvement of the native androgen receptor in the regulation by DHT of mACON gene expression. A stable-transfected clone that expresses the full-length androgen receptor was selected and termed PCAR9. The results revealed that DHT-treated PCAR9 cells paradoxically not only reduced the enzymatic activity of mACON but also blocked the biosynthesis of intracellular ATP attenuating cell proliferation. Transient gene expression assay indicated that DHT divergently regulates the promoter activity of the mACON gene in LNCaP and PCAR9 cells. This study suggested that DHT regulates mACON gene expression and the proliferation of cells in a receptor-dependent model through modulation by unidentified non-receptor factors.
Department of Anatomy, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, Republic of China. hhj143@mail.cgu.edu.tw
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D000154:Aconitate Hydratase / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017931:DNA Primers; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000502:physiology*; D014162:Transfection
D017931:DNA Primers; D011944:Receptors, Androgen; D013739:Testosterone; D015500:Chloramphenicol O-Acetyltransferase; D000154:Aconitate Hydratase