Expression of cancer/testis antigens in prostate cancer is associated with disease progression.
BACKGROUND
The cancer/testis antigens (CTAs) are a unique group of proteins normally expressed in germ cells but aberrantly expressed in several types of cancers including prostate cancer (PCa). However, their role in PCa has not been fully explored.


METHODS
CTA expression profiling in PCa samples and cell lines was done utilizing a custom microarray that contained probes for two-thirds of all CTAs. The data were validated by quantitative PCR (Q-PCR). Functional studies were carried out by silencing gene expression with siRNA. DNA methylation was determined by methylation-specific PCR.


RESULTS
A majority of CTAs expressed in PCa are located on the X chromosome (CT-X antigens). Several CT-X antigens from the MAGEA/CSAG subfamilies are coordinately upregulated in castrate-resistant prostate cancer (CRPC) but not in primary PCa. In contrast, PAGE4 is highly upregulated in primary PCa but is virtually silent in CRPC. Further, there was good correlation between the extent of promoter DNA methylation and CTA expression. Finally, silencing the expression of MAGEA2 the most highly upregulated member, significantly impaired proliferation of prostate cancer cells while increasing their chemosensitivity.


CONCLUSIONS
Considered together, the remarkable stage-specific expression patterns of the CT-X antigens strongly suggests that these CTAs may serve as unique biomarkers that could potentially be used to distinguish men with aggressive disease who need treatment from men with indolent disease not requiring immediate intervention. The data also suggest that the CT-X antigens may be novel therapeutic targets for CRPC for which there are currently no effective therapeutics.
Suyama
Takahito
T
Department of Urology, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Shiraishi
Takumi
T
Zeng
Yu
Y
Yu
Wayne
W
Parekh
Nehal
N
Vessella
Robert L
RL
Luo
Jun
J
Getzenberg
Robert H
RH
Kulkarni
Prakash
P
D000941:Antigens / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D013737:Testis / Q000276:immunology* / Q000473:pathology
D000941:Antigens; D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D012313:RNA; D004247:DNA