Quantitative expression profile of androgen-regulated genes in prostate cancer cells and identification of prostate-specific genes.
Quantitative expression profile of androgen-regulated genes (ARGs) was evaluated in the hormone-responsive prostate cancer cell line LNCaP by serial analysis of gene expression (SAGE). A total of 83,489 SAGE tags representing 23,448 known genes or expressed sequence tags (ESTs) and 1,655 potentially novel sequences have unraveled the transcriptome of LNCaP cells, the most common cell line used in prostate cancer research. Comparison of transcripts between control and R1881-treated LNCaP cells revealed the induction of 136 genes and repression of 215 genes in response to androgen (p < 0.05). Strikingly, a high fraction ( approximately 90%) of ARGs identified in our study has not been described as ARGs previously. A number of prostate-specific transcription factors were among the ARGs identified here. Classification of the ARGs on the basis of biochemical functions revealed that a great majority of ARGs identified in our experimental system appear to be involved in regulation of transcription, splicing, ribosomal biogenesis, mitogenesis, bioenergetics and redox processes. One of the novel aspects of androgen signaling included androgen regulation of genes involved in DNA repair/recombination process. By comparing our LNCaP-C and LNCaP-T SAGE libraries with SAGE tag libraries available at the NCBI-SAGE website, we have identified >200 potential prostate specific/abundant transcripts. The discovery of new prostate-specific genes and ARGs provides a unique opportunity to determine the role of these genes in prostate cell growth, differentiation and tumorigenesis.
Xu
L L
LL
Center for Prostate Disease Research (CPDR), Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Su
Y P
YP
Labiche
R
R
Segawa
T
T
Shanmugam
N
N
McLeod
D G
DG
Moul
J W
JW
Srivastava
S
S
D000728:Androgens / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D009928:Organ Specificity / Q000235:genetics; D011467:Prostate; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D045165:Testosterone Congeners / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000728:Androgens; D000951:Antigens, Neoplasm; C412325:SAGE1 protein, human; D045165:Testosterone Congeners; D015741:Metribolone