ALTERNATIVE SPLICING OF FIBROBLAST-GROWTH-FACTOR-RECEPTOR-2 (FGF-R2) IN HUMAN PROSTATE-CANCER

Progression of prostate cancer from sensitive to androgen insensitive tumor been shown to be accompanied by a change in alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) in a rat model of pro state cancer, This change results in loss of the FGF-R2(IIIb) isoform and predominant expression of the FGF-R2(IIIc) isoform, We sought to d etermine whether this change in FGF-R2 splicing is also associated wit h androgen insensitivity in human prostate tumors, We analysed three w eb characterized human prostate cancer cell lines and three metastatic prostate tumors which have been maintained as xenografts in nude mice , One of the cell lines, LNCaP, and two of the xenografts, DUKAP-1 and DUKAP-2, have been characterized as androgen sensitive, whereas two o f the cell lines, DU-145 and PC-3, and one of the xenografts, DU9479, display androgen independent growth, Using an RT-PCR based assay, me d emonstrated that progressive loss of the FGF-R2(111b) isoform correlat ed with androgen insensitivity in these human prostate cancer models. These findings lend support to the hypothesis that that loss of FGF-R2 (IIIb) may be one step in a series of events which lead to progression of human prostate cancer.