Identification of candidate prostate cancer genes through comparative expression-profiling of seminal vesicle.
BACKGROUND
Prostate cancer is the most frequently diagnosed cancer among men in the United States. In contrast, cancer of the seminal vesicle is exceedingly rare, despite that the prostate and seminal vesicle share similar histology, secretory function, androgen dependency, blood supply, and (in part) embryonic origin. We hypothesized that gene-expression differences between prostate and seminal vesicle might inform mechanisms underlying the higher incidence of prostate cancer.


METHODS
Whole-genome DNA microarrays were used to profile gene expression of 11 normal prostate and 7 seminal vesicle specimens (including six matched pairs) obtained from radical prostatectomy. Supervised analysis was used to identify genes differentially expressed between normal prostate and seminal vesicle, and this list was then cross-referenced to genes differentially expressed between normal and cancerous prostate. Expression patterns of selected genes were confirmed by immunohistochemistry using a tissue microarray.


RESULTS
We identified 32 genes that displayed a highly statistically significant expression pattern with highest levels in seminal vesicle, lower levels in normal prostate, and lowest levels in prostate cancer. Among these genes was the known candidate prostate tumor suppressor GSTP1 (involved in xenobiotic detoxification). The expression pattern of GSTP1 and four other genes, ABCG2 (xenobiotic transport), CRABP2 (retinoic acid signaling), GATA3 (lineage-specific transcription), and SLPI (immune response), was confirmed by immunohistochemistry.


CONCLUSIONS
Our findings identify candidate prostate cancer genes whose reduced expression in prostate (compared to seminal vesicle) may be permissive to prostate cancer initiation. Such genes and their pathways may inform mechanisms of prostate carcinogenesis, and suggest new opportunities for prostate cancer prevention.
Thompson
Maxwell
M
Department of Pathology, Stanford University, Stanford, California 94305-5176, USA.
Lapointe
Jacques
J
Choi
Yoon-La
YL
Ong
David E
DE
Higgins
John P
JP
Brooks
James D
JD
Pollack
Jonathan R
JR
D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012669:Seminal Vesicles / Q000502:physiology*
D009363:Neoplasm Proteins