Alterations in expression of basic fibroblast growth factor (FGF) 2 and its receptor FGFR-1 in human prostate cancer.
Fibroblast growth factors (FGFs) play an important role in the growth and maintenance of the normal prostate. There is increasing evidence from both animal models and analysis of human prostate cancer cell lines that alterations of FGFs and/or FGF receptors (FGFRs) may play an important role in prostate cancer progression. To better define the role of FGF2 and FGF7 in human prostate cancer in vivo, we have quantified these two growth factors in clinically localized human prostate cancers and uninvolved prostate by ELISA and Western blotting and determined their localization by immunohistochemistry. The expression of two of the primary receptors for these growth factors, FGFR-1 and FGFR-2, were also analyzed by immunohistochemistry and Western blotting in these same samples. We have found that FGF2 is significantly increased in prostate cancers when compared with uninvolved prostate and that the FGF2 is present in the stromal fibroblasts and endothelial cells but not the cancer cells. In addition, we have observed overexpression of both FGFR-1 and FGFR-2 in the prostate cancer epithelial cells in a subset of prostate cancers and that such overexpression is correlated with poor differentiation. Thus, there is both an increase in FGF2 concentration in prostate cancers and an increased expression of a receptor capable of responding to this growth factor, establishing a potential paracrine stimulation of prostate cancer cells by the surrounding stromal cells, which may play an important role in prostate cancer progression.
Giri
D
D
Department of Pathology, Baylor College of Medicine and Houston Department of Veterans Affairs Medical Center, Texas 77030, USA.
Ropiquet
F
F
Ittmann
M
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002846:Chromatography, Affinity; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology; D014407:Tumor Cells, Cultured
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D009363:Neoplasm Proteins; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2