Adenovirus-mediated expression of a soluble fibroblast growth factor receptor inhibits in vitro growth of prostate DU145 cells.
BACKGROUND
Fibroblast growth factor (FGF) family plays a key role in prostate cancer. The soluble FGF receptor (sFGFR) has been studied with regards to inhibiting cancer growth and was shown to have a dominant negative effect on cellular signaling and function. Using replication deficient adenovirus-mediated gene transfer, we tested if sFGFR expression may have a suppressive effect on in vitro growth of prostate cancer cells.


METHODS
Western analysis was used to verify expression of sFGFR1 and to examine the effect of sFGFR1 on MAP kinase phosphorylation. The effect on proliferation and invasiveness of DU145 cells was examined using the WST-1 and Matrigel Invasion assay, respectively.


RESULTS
Activation of MAP kinase (pERK1 and 2) by exogenous FGF1, 2, and 7 was suppressed to baseline levels by sFGFR, which was not seen with EGF. Proliferation and invasion of DU145 cells were significantly suppressed by sFGFR.


CONCLUSIONS
A replication deficient adenoviral vector system reproducibly expresses sFGFR in prostate cells. Suppression of in vitro growth in DU145 cells by sFGFR provides the basis of a novel therapeutic approach.
Prostate Research Group, School of Surgical and Reproductive Sciences, University of Newcastle, Newcastle, United Kingdom.
Bharat
B
Gowardhan
Alaiyi F
AF
West
Craig N
CN
Robson
Hing Y
HY
Leung
D000256:Adenoviridae / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011509:Proteoglycans / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D013778:Tetrazolium Salts / Q000494:pharmacology
C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; D013778:Tetrazolium Salts; C059485:matrigel; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases