Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer

Breast Cancer Res Treat. 2012 Jun;133(3):997-1008. doi: 10.1007/s10549-011-1883-6. Epub 2011 Nov 29.

Abstract

Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-β-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P < 0.01; Spearman correlation) between FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Humans
  • Mammary Glands, Animal / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, Nude
  • Mice, SCID
  • Middle Aged
  • Pregnancy
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism*
  • Transplantation, Heterologous

Substances

  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3