Liprin-alpha2 gene, protein tyrosine phosphatase LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP.
Prostate cancer is one of the most common neoplasms in the USA and Europe. We used differential display PCR (DD-PCR) to identify androgen-regulated genes in prostate cancer. The RNA of LNCaP cells treated with dihydrotestosterone (DHT) was analyzed for differentially expressed genes. Using DD-PCR, we identified a down-regulated cDNA fragment by DHT in LNCaP cells. This fragment was cloned and expressions of this fragment in prostate cancer cell lines were analyzed by RT-PCR. Sequence analysis revealed that a cDNA fragment is identical to protein tyrosine phosphatase LAR related gene, liprin-alpha2. liprin-alpha2 was downregulated by dihydrotestosterone (DHT) in LNCaP cells in a time- and androgen concentration-dependent manner. Downregulation by DHT was not inhibited by the protein synthesis inhibitor cycloheximide. This liprin-alpha2 gene was not expressed in androgen independent prostate cancer cell lines PC-3 and DU-145 at the mRNA level. And also, we first revealed here that liprin-alpha2 mRNA is expressed in LNCaP cells as well as human prostate cancer tissues and normal prostate tissues. These data suggest that liprin-alpha2 might play a role in androgen responsive human prostate cancer cell line as well as human prostate cells, and the loss of this gene expression might be associated with the androgen independent characteristics of prostate cancer.
Department of Urology, Yokohama City University, Yokohama, Japan.
Kiyoshi
K
Fujinami
Hiroji
H
Uemura
Hitoshi
H
Ishiguro
Yoshinobu
Y
Kubota
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000728:Androgens; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000728:Androgens; D018076:DNA, Complementary; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C470384:PPFIA2 protein, human; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013196:Dihydrotestosterone; D003513:Cycloheximide