Progression of prostate cancer from an androgen sensitive to androgen insensitive tumor has previously been shown to be accompanied by a change in alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) in a rat model of prostate cancer. This change results in loss of the FGF-R2(IIIb) isoform and predominant expression of the FGF-R2(IIIc) isoform. We sought to determine whether this change in FGF-R2 splicing is also associated with androgen insensitivity in human prostate tumors. We analysed three well 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 of the cell lines, DU-145 and PC-3, and one of the xenografts, DU9479, display androgen independent growth. Using an RT-PCR based assay, we demonstrated that progressive loss of the FGF-R2(IIIb) isoform correlated with androgen insensitivity in these human prostate cancer models. These findings lend support to the hypothesis that that loss of FGF-RZ(IIIb) may be one step in a series of events which lead to progression of human prostate cancer.
Bibliographical noteFunding Information:
We thank members of the Garcia-Blanco laboratory for helpful advice and suggestions and the Keck foundation for support of the Leon Levine Science Research Center where much of this research was performed. This work was supported by an NIH grant and the Research Discovery Grant of the Duke Comprehensive Cancer Center to MAGB. RPC was supported by an NIDDK training grant.
- Alternative splicing
- Androgen sensitivity
- Fibroblast growth factor receptors
- Prostate cancer
- Xenograft cell lines