Exon III Splicing of Fibroblast Growth Factor Receptor 1 Is Modulated by Growth Factors and Cyclin D1
- 1 August 2008
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Pancreas
- Vol. 37 (2), 159-164
- https://doi.org/10.1097/mpa.0b013e31816618a4
Abstract
Fibroblast growth factor receptor 1 (FGFR1) isoform IIIc enhances and FGFR1-IIIb inhibits pancreatic cancer cell growth. Nothing is presently known about the expression and regulation of human FGFR1-III isoforms. The aim of this study was to identify regulators modulating the specific expression of human FGFR1-IIIb and FGFR1-IIIc. Parental cells, cells overexpressing FGFR1-III isoforms, and cells harboring a tetracycline-inducible cyclin D1 antisense expression vector system were used as model systems. FGFR1-IIIb and -IIIc were coexpressed in human pancreatic cancer cells, with FGFR1-IIIc being the predominant isoform. FGFR1-IIIb mRNA expression decreased at higher cell density, whereas FGFR1-IIIc expression remained constant. Insulinlike growth factor I and epidermal growth factor induced expression of FGFR1-IIIc without altering FGFR1-IIIb. In contrast, fibroblast growth factor (FGF)1, FGF2, and FGF5 induced FGFR1-IIIc and reduced the expression of FGFR1-IIIb. Overexpression of one isoform did not alter the expression of the corresponding FGFR1-III isoform. Inhibition of cyclin D1, known to be induced by insulinlike growth factor I, epidermal growth factor, and FGF2, resulted in an inhibition of FGFR1-IIIc expression, whereas FGFR1-IIIb expression was enhanced. This study demonstrated for the first time that FGFR1-IIIb and FGFR1-IIIc are coexpressed and that the FGFR1-III isoformsare differentially regulated by growth factors and cyclin D1.Keywords
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