Abstract
BackgroundSingle Nucleotide Polymorphisms (SNPs) in intron 2 of the Fibroblast Growth Factor Receptor Type 2 (FGFR2) gene, including rs2981582, contribute to multifactorial breast cancer susceptibility. The high risk polymorphism haplotype in the FGFR2 gene has been associated with increased mRNA transcription and altered transcription factor binding but the effect on FGFR2 protein expression is unknown. 40 breast tumours were identified from individuals with known rs2981582 genotype. Tumour sections were stained for FGFR2 protein expression, and scored for nuclear and cytoplasmic staining in tumour and surrounding normal tissue.FindingsFGFR2 immunohistochemistry demonstrated variable nuclear staining in normal tissue and tumour tissue, as well as consistent cytoplasmic staining. We did not find an association between nuclear staining for FGFR2 and genotype, and there was no association between FGFR2 staining and estrogen or progestogen receptor status. There was an association between presence of nuclear staining for FGFR2 in normal tissue and presence of nuclear staining in the adjacent tumour (Fishers exact test, p = 0.002).ConclusionsVariable nuclear staining for FGFR2 in breast cancer, but an absence of correlation with rs2981582 genotype suggests that the mechanism of action of polymorphisms at the FGFR2 locus may be more complex than a direct effect on mRNA expression levels in the final cancer. The effect may relate to FGFR2 function or localisation during breast development or tumourigenesis. Nuclear localisation of FGFR2 suggests an important additional role for this protein in breast development and breast cancer, in addition to its function as a classical cell surface receptor.
Highlights
Single Nucleotide Polymorphisms (SNPs) in intron 2 of the Fibroblast Growth Factor Receptor Type 2 (FGFR2) gene, including rs2981582, contribute to multifactorial breast cancer susceptibility
Variable nuclear staining for FGFR2 in breast cancer, but an absence of correlation with rs2981582 genotype suggests that the mechanism of action of polymorphisms at the FGFR2 locus may be more complex than a direct effect on mRNA expression levels in the final cancer
Fibroblast growth factor receptor type 2 (FGFR2) is a receptor tyrosine kinase involved in a number of cell signalling pathways that contribute to cell growth and differentiation [1]
Summary
Single Nucleotide Polymorphisms (SNPs) in intron 2 of the Fibroblast Growth Factor Receptor Type 2 (FGFR2) gene, including rs2981582, contribute to multifactorial breast cancer susceptibility. The high risk polymorphism haplotype in the FGFR2 gene has been associated with increased mRNA transcription and altered transcription factor binding but the effect on FGFR2 protein expression is unknown. Recent interest has focussed on Single Nucleotide Polymorphisms (SNPs) in intron 2 of FGFR2 , including rs2981582, which form a high risk haplotype that is principally considered a cell surface receptor, FGFR2 is found to have nuclear localisation in a number of different breast and cancer related contexts [7,8]. The related receptor FGFR1 has been shown to be transported actively to the nucleus, where it may act as a transcription factor coordinating gene expression and promoting cellular differentiation [9]. FGFR2 has been has been identified in the terminal end buds during mammary gland development, with nuclear localisation [8], suggesting that the nuclear localisation plays an important role in breast development
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.