Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer.
A novel gene, prostate cancer antigen (PCA)-1, was recently reported to be expressed in the prostate; however, its biological roles remain unclear. Knockdown of the PCA-1 gene by small interfering RNA transfection induced apoptosis through reducing the expression of the anti-apoptotic molecule Bcl-xl and cytoplasmic release of cytochrome c in the androgen-independent prostate cancer cell line PC3. Moreover, in vitro matrigel and in vivo chorioallantoic membrane assays showed that silencing of PCA-1 significantly downregulated discoidin receptor (DDR)-1 expression, resulting in suppression of cancer-cell invasion. Transfection with PCA-1 increased the levels of both Bcl-xl and DDR1, which made the cells more invasive through the upregulation of matrix metalloproteinase 9 in DU145. Interestingly, long-term culture using androgen-free medium increased the level of PCA-1 and the related expression of Bcl-xl and DDR-1 in the androgen-sensitive cancer cell line LNCaP, suggesting that PCA-1 signaling is associated with androgen independence. Immunohistochemical analysis in a series of 169 prostate carcinomas showed that PCA-1 and DDR1 were strongly expressed in prostate cancer cells, including preneoplastic lesions, but there was little or no expression in normal epithelium. Moreover, the expression of PCA-1 and DDR-1 was associated with a hormone-independent state of prostate cancer. Taken together, we propose that PCA-1-DDR-1 signaling is a new important axis involved in malignant potential prostate cancer associated with hormone-refractory status.
Shimada
Keiji
K
Department of Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Nakamura
Mitsutoshi
M
Ishida
Eiwa
E
Higuchi
Tomonori
T
Yamamoto
Hiroshi
H
Tsujikawa
Kazutake
K
Konishi
Noboru
N
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival; D002642:Chick Embryo; D000070818:Discoidin Domain Receptors; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011975:Receptors, Mitogen / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
D000951:Antigens, Neoplasm; C494811:BCL2L1 protein, human; C505096:PCA-1 antigen, human; D012333:RNA, Messenger; D011975:Receptors, Mitogen; D051020:bcl-X Protein; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020780:Matrix Metalloproteinase 9