FGFR1 is essential for prostate cancer progression and metastasis

Feng Yang, Yongyou Zhang, Steven J. Ressler, Michael M. Ittmann, Gustavo E. Ayala, Truong D. Dang, Fen Wang, David R. Rowley

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The fibroblast growth factor receptor 1 (FGFR1) is ectopically expressed in prostate carcinoma cells, but its functional contributions are unde fined. In this study, we report the evaluation 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.

Original languageEnglish (US)
Pages (from-to)3716-3724
Number of pages9
JournalCancer research
Volume73
Issue number12
DOIs
StatePublished - Jun 15 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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