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

Guowei Chen1, Jian Wang, Zhanbing Liu

  • 1Department of General, Visceral, and Transplantation Surgery, University of Ulm, Ulm, Germany.

Pancreas
|July 31, 2008
PubMed
Abstract

Insights

Fibroblast growth factor receptor 1 (FGFR1) isoforms IIIb and IIIc are coexpressed in pancreatic cancer. Growth factors and cyclin D1 differentially regulate these FGFR1 isoforms, impacting cancer cell growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Fibroblast growth factor receptor 1 (FGFR1) has distinct isoforms, FGFR1-IIIb and FGFR1-IIIc, with opposing effects on pancreatic cancer cell growth.
  • The expression and regulation of these specific human FGFR1 isoforms remain largely uncharacterized.

Purpose of the Study:

  • To investigate the regulators that modulate the specific expression of human FGFR1-IIIb and FGFR1-IIIc.
  • To understand the differential expression patterns of FGFR1 isoforms in pancreatic cancer.

Main Methods:

  • Utilized parental cells, cells overexpressing FGFR1-III isoforms, and a tetracycline-inducible cyclin D1 antisense system.
  • Analyzed the expression of FGFR1-IIIb and FGFR1-IIIc under varying cell densities and in response to specific growth factors (IGF-I, EGF, FGF1, FGF2, FGF5).

Main Results:

  • FGFR1-IIIb and FGFR1-IIIc were coexpressed in human pancreatic cancer cells, with FGFR1-IIIc being predominant.
  • FGFR1-IIIc expression was induced by IGF-I, EGF, FGF1, FGF2, and FGF5, while FGFR1-IIIb expression was reduced by FGF1, FGF2, and FGF5.
  • Inhibition of cyclin D1 led to decreased FGFR1-IIIc expression and enhanced FGFR1-IIIb expression.

Conclusions:

  • Demonstrated coexpression of FGFR1-IIIb and FGFR1-IIIc in human pancreatic cancer.
  • Established that FGFR1-III isoforms are differentially regulated by specific growth factors and cyclin D1, providing insights into pancreatic cancer progression.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...