Differential Expression of the Fibroblast Growth Factor Receptor (FGFR) Multigene Family in Normal Human Adult Tissues

Abstract

SUMMARY This report describes a systematic analysis of the expression of the fibroblast growth factor receptor (FGFR) multigene family (FGFR1, FGFR2, FGFR3, and FGFR4) in archival serial sections of normal human adult tissues representing the major organ systems, using immunohistochemical techniques. Polyclonal antisera specific for FGFR1, FGFR2, FGFR3, and FGFR4 and a three-stage immunoperoxidase technique were employed to determine the cellular distribution of these receptors at the protein level. The expression profiles for the tissue-specific cellular localization of the FGFR multigene family demonstrated widespread and striking differential patterns of expression of individual receptors in the epithelia and mesenchyme of multiple tissues (stomach, salivary glands, pancreas, thymus, ureter, and cornea) and co-expression of FGFR1-4 in the same cell types of other tissues. The widespread expression of FGFR1-4 in multiple organ systems suggests an important functional role in normal tissue homeostasis. Differences in the spatial patterns of FGFR gene expression may generate functional diversity in response to FGF-1 and FGF-2, both of which bind with equally high affinity to more than one receptor subtype. In vivo, this may lead to functional differences that are crucial for the regulation of normal physiological processes and are responsible for the pathological mechanisms that orchestrate various disease processes. (J Histochem Cytochem 45:1005-1019, 1997)

Genetically defined mouse models that mimic natural aspects of human prostate cancer development.

“…It is also interesting that prostate appears to exhibit wide expression of the general classes of FGFRs. For example, a moderate level of expression of FGFR1 and FGFR2 is found in prostate epithelium and the microvasculature, while stromal smooth muscle cells exhibit a weak level of expression of FGFR3 (Hughes 1997). In another study (Ittman & Mansukhani 1997), in primary cultures of human prostate epithelial and stromal cells, FGFR3 was found to be the primary product in epithelial cells with smaller amount of FGFR2, while stromal cells express primarily FGFR3 and small amounts of FGFR1 and FGFR2.…”

FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease

“…Fgfr1 is expressed in the calvarial mesenchyme and later in osteoblasts, whereas Fgfr2 is expressed at sites of ossification in differentiating osteoblasts (Hughes 1997;Britto et al 1998Britto et al , 2001bDelezoide et al 1998;Ohbayashi et al 2002). Fgfr3 is not found in calvarial mesenchymal cells or periosteal cells but is detected at low levels in sutural osteogenic fronts at late stages of development Molteni et al 1999;Marie et al 2000;Rice et al 2000).…”

High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes

“…FGFR1, which belongs to a family of four receptor tyrosine kinases, is a 92 kDa transmembrane protein with an extracellular domain containing three immunoglobulin-like C2-type domains, a heparin-binding site, a transmembrane domain and an intracellular thyrosine kinase domain (Eswarakumar et al, 2005). FGFR1 is expressed in most tissues including normal fetal and adult salivary gland tissue (Hughes, 1997;Hoffman et al, 2002). Interestingly, FGFR1 is also involved in the development of salivary glands by regulation of branching morphogenesis (Hoffman et al, 2002).…”