ASAP1, a gene at 8q24, is associated with prostate cancer metastasis.
Metastatic prostate cancer is a terminal disease, and the development of reliable prognostic tools and more effective therapy is critically important for improved disease survival and management. This study was aimed at identifying genes that are differentially expressed in metastatic and nonmetastatic prostate cancer cells and, as such, could be critical in the development of metastasis. Long-SAGE analysis was used to compare a transplantable human metastatic prostate cancer subline, PCa1-met, with a nonmetastatic counterpart, PCa2. Both sublines were developed from a patient's prostate cancer specimen via subrenal capsule grafting and subsequent orthotopic implantation into SCID mice. Among various differentially expressed genes identified, ASAP1, an 8q24 gene encoding an ADP-ribosylation factor GTPase-activating protein not previously associated with prostate cancer, was up-regulated in the metastatic subline as confirmed by quantitative real-time PCR. Immunohistochemistry of xenograft sections showed that cytoplasmic ASAP1 protein staining was absent or weak in benign tissue, significantly stronger in nonmetastatic PCa2 tissue, and strongest in PCa1-met tissue. In clinical specimens, ASAP1 protein staining was elevated in 80% of primary prostate cancers and substantially higher in metastatic lesions compared with benign prostate tissue. Moreover, additional ASAP1 gene copies were detected in 58% of the primary prostate cancer specimens. Small interfering RNA-induced reduction of ASAP1 protein expression markedly suppressed in vitro PC-3 cell migration (approximately 50%) and Matrigel invasion (approximately 67%). This study suggests that the ASAP1 gene plays a role in prostate cancer metastasis and may represent a therapeutic target and/or biomarker for metastatic disease.
Department of Cancer Endocrinology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Dong
D
Lin
Akira
A
Watahiki
Jane
J
Bayani
Fang
F
Zhang
Lin
L
Liu
Victor
V
Ling
Marianne D
MD
Sadar
John
J
English
Ladan
L
Fazli
Alan
A
So
Peter W
PW
Gout
Martin
M
Gleave
Jeremy A
JA
Squire
Yu-Zhuo
YZ
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013347:Subcellular Fractions
C117891:ASAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers