Exon III splicing of fibroblast growth factor receptor 1 is modulated by growth factors and cyclin D1.

Abstract

OBJECTIVES:

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.

METHODS:

Parental cells, cells overexpressing FGFR1-III isoforms, and cells harboring a tetracycline-inducible cyclin D1 antisense expression vector system were used as model systems.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Guowei Chen, Jian Wang, Zhanbing Liu, Marko Kornmann
• Journal: Pancreas (Pancreas) Vol. 37 Issue 2 Pg. 159-64 (Aug 2008) ISSN: 1536-4828 [Electronic] United States
• PMID: 18665077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• FGF5 protein, human
• Growth Substances
• Protein Isoforms
• Fibroblast Growth Factor 2
• Fibroblast Growth Factor 1
• Fibroblast Growth Factor 5
• Cyclin D1
• Insulin-Like Growth Factor I
• FGFR1 protein, human
• Receptor, Fibroblast Growth Factor, Type 1

Topics

• Alternative Splicing (drug effects)
• Base Sequence
• Cell Line, Tumor
• Cyclin D1 (antagonists & inhibitors, genetics, metabolism)
• DNA Primers (genetics)
• Exons
• Fibroblast Growth Factor 1 (metabolism, pharmacology)
• Fibroblast Growth Factor 2 (metabolism, pharmacology)
• Fibroblast Growth Factor 5 (metabolism, pharmacology)
• Growth Substances (metabolism, pharmacology)
• Humans
• Insulin-Like Growth Factor I (metabolism, pharmacology)
• Pancreatic Neoplasms (genetics, metabolism)
• Protein Isoforms (genetics)
• Receptor, Fibroblast Growth Factor, Type 1 (genetics)