High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity.
The expression of cutaneous fatty acid-binding protein (C-FABP) in prostate tissues was examined by immunohistochemistry. Among the 76 cases, all seven (100%) normal tissues were unstained. Of the 35 benign prostatic hyperplasia (BPH), 25 (71.4%) specimens were unstained and 10 (28.6%) were stained positively. For the 34 prostatic carcinomas, the C-FABP expression was remarkably increased: 25 (73.5%) samples stained positively, and only nine (26.5%) were unstained. Transfection of a vector expressing an antisense C-FABP transcript into the PC-3M prostatic cancer cells yielded two transfectant lines: PC-3M-CFABP-1 and PC-3M-CFABP-3, producing, respectively, a 3.8- and a 6.9-fold reduction in C-FABP levels. Comparing with the control transfectants, the in vitro invasiveness of both PC-3M-CFABP-1 and PC-3M-CFABP-3 was significantly reduced. When tested in nude mouse, the average size of tumours produced by PC-3M-CFABP-1 and by PC-3M-CFABP-3 was reduced by 2.9- and 4.2-fold respectively, in comparison with that of tumours produced by the control transfectants. Analysis showed that the decreased vascular endothelial growth factor (VEGF) and microvessel densities in the tumours were associated with the reduced C-FABP. These data show that C-FABP is increased in prostatic carcinoma cells and suppression of its expression can significantly inhibit the tumorigenicity, probably by reducing the expression of VEGF.
Adamson
Janet
J
Molecular Pathology Laboratory, Department of Pathology, Faculty of Medicine, University of Liverpool, Liverpool L69 3BX, UK.
Morgan
Elwin A
EA
Beesley
Carol
C
Mei
Yongqiang
Y
Foster
Christopher S
CS
Fujii
Hiroshi
H
Rudland
Philip S
PS
Smith
Paul H
PH
Ke
Youqiang
Y
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics; D005169:Factor VIII / Q000235:genetics; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008222:Lymphokines / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D002352:Carrier Proteins; D016228:Endothelial Growth Factors; C107608:FABP7 protein, human; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005169:Factor VIII