Differently regulated androgen receptor transcriptional complex in prostate cancer compared with normal prostate.
BACKGROUND
The coregulators of androgen receptors (AR) influence the transcriptional activity of AR. In order to better understand the mechanism of carcinogenesis in the prostate, we investigated the relationship between AR and AR coregulators in the early stage of prostate cancer.


METHODS
mRNA was purified from 15 samples of prostate cancer and normal tissue and transcribed into cDNA. We screened eight AR coregulators for different gene expressions in prostate cancer, comparing these with normal tissue by a real-time polymerase chain reaction Syber green method, then quantified each component of the AR transcriptional complex by a real-time PCR hybri-probe method. The extent of gene expression similarity was compared by simple Pearson correlation coefficient analysis between prostate cancer and normal tissue. We applied a z-test to calculate significant differences between r-values.


RESULTS
We found that the gene expression level of FHL2 decreased in prostate cancer compared with that of normal tissue and the gene expressions of PSA, AR and SMRT were not significant. The correlation coefficient analysis revealed that strong associations were found in the pairs of AR versus SMRT, AR versus FHL2 and SMRT versus FHL2 in prostate cancer, whereas similarity was found only in the pair of AR versus FHL2 in normal tissue. No association was observed between prostate-specific antigen and other genes.


CONCLUSIONS
These results demonstrate that the AR-AR coregulator relationship is different between prostate cancer and normal tissue, leading to the hypothesis that the AR transcriptional complex is regulated differently between prostate cancer and normal tissue.
Kinoshita
Masashige
M
Department of Urology, Osaka Medical College, Takatsuki City, Osaka, Japan.
Nakagawa
Toshimasa
T
Shimizu
Akira
A
Katsuoka
Yoji
Y
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D056985:Nuclear Receptor Co-Repressor 2; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D012334:RNA, Neoplasm; D011944:Receptors, Androgen; D012097:Repressor Proteins; D014157:Transcription Factors; D017430:Prostate-Specific Antigen