Tissue distribution and retinoid-mediated downregulation of an FGF-binding protein (FGF-BP) in the rat.
We showed previously that a secreted fibroblast growth factor-binding protein (FGF-BP) can mobilize and bioactivate locally-stored FGFs from the extracellular matrix. This FGF-BP is upregulated in various cancers and plays a rate limiting role as an angiogenic switch molecule during tumor growth. In this paper, we describe the cloning and sequence analysis of the rat homologue of FGF-BP and show its expression pattern and retinoid-mediated downregulation in normal adult rat tissues. The rat FGF-BP amino acid sequence is 91% and 70% homologous to mouse and human, respectively, and contains 10 cysteine residues whose position is conserved across species. In Northern blots, FGF-BP mRNA was detected in the gut, eye, thymus, skin, lung and tongue. Immunohistochemistry confirmed this tissue distribution with cerebellar Purkinje cells, the cerebral chorioid plexus and the eye showing the most distinctive staining patterns. Oral treatment of animals with all-trans-retinoic acid for one and two days induced a significant decrease of FGF-BP protein in tissues from stomach, eye and lung suggesting that regulation of FGF-BP can be one effector mechanism through which retinoids affect normal and pathological processes.
Aigner
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A
Lombardi Cancer Center and Department of Pharmacology, Georgetown University, Washington, DC 20007, USA. aigner@mailer.uni-marburg.de
Malerczyk
C
C
Houghtling
R
R
Wellstein
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A
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*
D002352:Carrier Proteins; C489453:Fgfbp1 protein, mouse; C489454:Fgfbp1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C070699:FGFBP1 protein, human; D014212:Tretinoin