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PMID: 7803853 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial-mesenchymal transition in rat bladder carcinoma cells.

Molecular biology of the cell ·Vol. 5 ·No. 8 ·1994-08-00 ·Pages 851-62

Savagner P, Vallés AM, Jouanneau J, Yamada KM, Thiery JP

Abstract

We described previously that acidic fibroblast growth factor (aFGF), but not basic fibroblast growth factor (bFGF), can induce the rat carcinoma cell line NBT-II to undergo a rapid and reversible transition from epithelial to mesenchymal phenotype (EMT). We now find that NBT-II EMT is stimulated by keratinocyte growth factor (KGF) in cells grown at low density. Accordingly, a high-affinity receptor showing 98% homology to mouse FGF receptor 2b/KGF receptor was cloned and sequenced from NBT-II cells. Northern analysis indicated that mRNA for FGF receptor 2b/KGF receptor was drastically down-regulated within 1 wk in aFGF-induced mesenchymal NBT-II cells. This decrease coincided with an up-regulation of FGF receptor 2c/Bek, a KGF-insensitive, alternatively spliced form of FGF receptor 2b/KGF receptor. Functional studies confirmed that KGF could not maintain EMT induction on mesenchymal NBT-II cells. FGF receptor 1 and FGF receptor 2c/Bek could also support EMT induction when transfected into NBT-II cells in response to aFGF or bFGF. Such transfected cells could bind bFGF as well as aFGF. Therefore, EMT can be induced through different FGF receptors, but EMT may also regulate FGF receptor expression itself.

MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Base Sequence DNA Primers/genetics Epithelium/metabolism,pathology Gene Expression Regulation, Neoplastic Humans Mesoderm/metabolism,pathology Mice Molecular Sequence Data Phenotype RNA, Messenger/genetics,metabolism Rats Receptor Protein-Tyrosine Kinases/genetics Receptor, Fibroblast Growth Factor, Type 1 Receptor, Fibroblast Growth Factor, Type 2 Receptors, Fibroblast Growth Factor/genetics Receptors, Growth Factor/genetics Sequence Homology, Amino Acid Transfection Tumor Cells, Cultured/metabolism,pathology Urinary Bladder Neoplasms/genetics,metabolism,pathology
Chemicals
DNA Primers RNA, Messenger Receptors, Fibroblast Growth Factor Receptors, Growth Factor FGFR1 protein, human FGFR2 protein, human Fgfr1 protein, mouse Fgfr1 protein, rat Fgfr2 protein, mouse Fgfr2 protein, rat Receptor Protein-Tyrosine Kinases Receptor, Fibroblast Growth Factor, Type 1 Receptor, Fibroblast Growth Factor, Type 2 keratinocyte growth factor receptor
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Savagner P
Laboratoire de Physiopathologie du Développement, Centre National de la Recherche Scientifique-Ecole Normale Supérieure, Paris, France.
Vallés A M
Jouanneau J
Yamada K M
Thiery J P
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.5.8.851
Published
1994-08-00
Pages
851-62
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC301106
Subset
IM
Grants
NCI NIH HHS · 2 R01 CA-49417-04 · United States
Databases
GENBANK
Z35137, Z35138, Z35139
External Links
PubMed source DOI: 10.1091/mbc.5.8.851 PMC Full Text View journal details
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