TY - JOUR
T1 - High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity
AU - Adamson, Janet
AU - Morgan, Elwin A
AU - Beesley, Carol
AU - Mei, Yongqiang
AU - Foster, Christopher S
AU - Fujii, Hiroshi
AU - Rudland, Philip S
AU - Smith, Paul H
AU - Ke, Youqiang
PY - 2003/5/8
Y1 - 2003/5/8
N2 - 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.
AB - 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.
KW - Animals
KW - Carrier Proteins
KW - Endothelial Growth Factors
KW - Factor VIII
KW - Fatty Acid-Binding Proteins
KW - Fatty Acids
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Immunohistochemistry
KW - Intercellular Signaling Peptides and Proteins
KW - Lymphokines
KW - Male
KW - Mice
KW - Mice, Nude
KW - Neoplasm Invasiveness
KW - Neoplasm Proteins
KW - Nerve Tissue Proteins
KW - Prostatic Neoplasms
KW - Recombinant Proteins
KW - Skin
KW - Transfection
KW - Transplantation, Heterologous
KW - Tumor Cells, Cultured
KW - Tumor Suppressor Proteins
KW - Vascular Endothelial Growth Factor A
KW - Vascular Endothelial Growth Factors
U2 - 10.1038/sj.onc.1206341
DO - 10.1038/sj.onc.1206341
M3 - Article
C2 - 12743598
SN - 0950-9232
VL - 22
SP - 2739
EP - 2749
JO - Oncogene
JF - Oncogene
IS - 18
ER -