title: FGFR1 is essential for prostate cancer progression and metastasis.
abstract: The fibroblast growth factor receptor 1 (FGFR1) is ectopically expressed in prostate carcinoma cells, but its functional contributions are undefined. In this study, we report the evaluation of a tissue-specific conditional deletion mutant generated in an ARR2PBi(Pbsn)-Cre/TRAMP/fgfr1(loxP/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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. fyang@bcm.edu
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Yongyou
authors.initials: Y
authors.lastname: Zhang
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ressler
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ittmann
authors.forename: Gustavo E
authors.initials: GE
authors.lastname: Ayala
authors.forename: Truong D
authors.initials: TD
authors.lastname: Dang
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: David R
authors.initials: DR
authors.lastname: Rowley
mesh_terms: D000818:Animals; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D051496:Receptor, Fibroblast Growth Factor, Type 1