The fibroblast growth factor receptor FGFR1 is ectopically expressed in prostate carcinoma cells, but its functional contributions are undefined.
In this study, we report the evalulation of a tissue-specific conditional deletion mutant generated in an ARR2PBi(Pbsn)-Cre/TRAMP/fgfr1loxP/loxP transgenic mouse model of prostate cancer. Mice lacking fgfr1 in prostate cells developed smaller tumors that also included distinct cancer foci still expressing fgfr1 indicating focal escape from gene excision. Tumors with confirmed fgfr1 deletion exhibited increased foci of early, well-differentiated cancer and phyllodes-type tumors, and tumors that escaped fgfr1 deletion primarily exhibited a poorly differentiated phenotype. Consistent with these phenotypes, mice carrying the fgfr1 null allele survived significantly longer than those without fgfr1 deletion. Most interestingly, all metastases were primarily negative for the fgfr1 null allele, exhibited high FgfR1 expression and a neuroendocrine phenotype regardless of fgfr1 status in the primary tumors. Together, these results suggest a critical and permissive role of ectopic FGFR1 signaling in prostate tumorigenesis and particularly in mechanisms of metastasis.
Written by:
Yang F, Zhang Y, Ressler SJ, Ittmann MM, Ayala GE, Dang TD, Wang F, Rowley DR. Are you the author?
Molecular and Cellular Biology, Baylor College of Medicine.
Reference: Cancer Res. 2013 Apr 10. Epub ahead of print.
doi: 10.1158/0008-5472.CAN-12-3274
PubMed Abstract
PMID: 23576558
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