Expression of cutaneous fatty acid-binding protein (C-FABP) in prostate cancer: potential prognostic marker and target for tumourigenicity-suppression.
C-FABP or E-FABP is a metastasis inducing gene over expressed in human prostate carcinomas. To study its prognostic significance, an archival set of prostate tissues was analysed immunohistochemically. Levels of both nuclear and cytoplasmic C-FABP expression in carcinoma cells were significantly higher than those in normal and BPH tissues and the increased C-FABP was significantly associated with a reduced patient survival time. To test the therapeutic potential of targeting C-FABP, a clone (Si-clone-2) of cells was established by interfering C-FABP expression in highly malignant PC-3M cells. Suppression of C-FABP in cancer cells significantly inhibited their proliferation and tumourigenicity in vitro. When Si-clone-2 cells were orthotopically implanted into the prostate gland of mouse, 2/13 mice produced primary tumours with an average size of 23+/-5 mg, and no metastasis was produced in any of the 13 animals. Whereas in the control group, all 14 mice produced primary tumours with an average size of 1450+/-370 mg and 9/14 (64.3%) produced metastasis. When inoculated subcutaneously, all 5 mice inoculated with control cells developed tumours from day 4, with an average size of 1471+/-544 mm(3) at 5 weeks after the inoculation; whereas Si-clone-2 cells produced no tumours in any of the 5 animals at any time-point, indicating the suppression occurred at the initiation stage. Our results suggest that C-FABP may be used as a potential prognostic marker to predict patient outcome and the increased C-FABP expression is a possible target to inhibit the malignant progression of prostate cancer cells.
Morgan
Elwin A
EA
Molecular Pathology Laboratory, School of Cancer Studies, Faculty of Medicine, the University of Liverpool, Liverpool, L69 3GA, UK.
Forootan
Shiva S
SS
Adamson
Janet
J
Foster
Christopher S
CS
Fujii
Hiroshi
H
Igarashi
Michihiro
M
Beesley
Carol
C
Smith
Paul H
PH
Ke
Youqiang
Y
D000818:Animals; D045744:Cell Line, Tumor; D050556:Fatty Acid-Binding Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000628:therapy; D034741:RNA, Small Interfering / Q000494:pharmacology
D050556:Fatty Acid-Binding Proteins; D034741:RNA, Small Interfering