Functional activity of epidermal growth factor receptors in
autosomal recessive polycystic kidney disease.
Sweeney, William E., and Ellis D. Avner.
Department of Pediatrics, Rainbow Babies and Children_s Hospital
and Case Western Reserve University, Cleveland Ohio
APStracts 5:0099F, 1998.
Evidence from a number of laboratories suggests a potential role for
the epidermal growth factor (EGF)/ transforming growth factor alpha
(TGF-[alpha])/ epidermal growth factor receptor (EGF-R) axis in
promoting epithelial hyperplasia, and cyst formation in ARPKD. As
previously reported, in the CPK, BPK, and ORPK murine models of
ARPKD, as well as in human ARPKD and human ADPKD, the EGF-R is
mislocated to the apical surface of cystic collecting tubule (CT)
epithelial cells. The present studies demonstrate that cells from
cystic and control CT can be isolated, and that these cells maintain
their in vivo EGF-R phenotype, in vitro. Domain specific high
affinity ligand binding was assessed by standard Scatchard analysis
and selective ligand stimulation of apical versus basolateral EGF-R
in these cells was followed by measurement of receptor
autophosphorylation, and determination of cell proliferation. These
studies demonstrate that, in vitro, apically expressed EGF-Rs exhibit
high affinity binding for EGF, autophosphorylate in response to EGF
and transmit a mitogenic signal when stimulated by the appropriate
ligand.
Received 28 January 1998; accepted in final form 13 May 1998.
APS Manuscript Number F19-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 16 June 1998