Human pHyde is not a classical tumor suppressor gene in prostate cancer.
A novel putative tumor suppressor gene, pHyde, was recently cloned from rat prostate. The rat gene has been shown to inhibit prostate cancer cell proliferation both in vitro and in vivo. However, the role of human pHyde in prostate cancer has not been studied before. Here, we analyzed human prostate cancer cell lines (LNCaP, DU145, PC-3, 22Rv1), xenografts (LuCaP 23.1, 35, 41, 49, 58, 69, 70 and 73) and clinical prostate carcinomas for genetic alterations and expression of pHyde. The expression of pHyde in normal human tissues as well as in prostate cancer was studied by Northern analysis and real-time quantitative RT-PCR. It was ubiquitously expressed in all normal tissues analyzed. Although, the expression was significantly (p=0.007) lower in poorly differentiated than in well and moderately differentiated carcinomas, there were no differences in the expression levels between benign prostate hyperplasia, untreated primary and recurrent hormone-refractory prostate carcinomas (p=0.607). Altogether, missense mutations were detected in 2 out of 68 samples studied ( approximately 3%) by denaturing high-performance liquid chromatography (DHPLC) and sequencing. One of the samples with the mutation also exhibited a loss of a gene copy by fluorescence in situ hybridization (FISH). This was the only sample that exhibited a genetic alteration in both alleles, suggesting that the human pHyde is not a classical prostate tumor suppressor gene. The reduced expression of the gene found in some tumors warrant further studies.
Porkka
Kati P
KP
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Nupponen
Nina N
NN
Tammela
Teuvo L J
TL
Vessella
Robert L
RL
Visakorpi
Tapio
T
D000818:Animals; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000502:physiology*; D010088:Oxidoreductases; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D017931:DNA Primers; D015513:Oncogene Proteins; D012333:RNA, Messenger; C437943:Steap3 protein, rat; D004247:DNA; D010088:Oxidoreductases; C486677:STEAP3 protein, human