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(Received for publication, May 20, 1997, and in revised form, August 27, 1997)
From the In this study we have examined the interaction
between CD44s (the standard form) and the p185HER2
proto-oncogene in the ovarian carcinoma cell line. Surface
biotinylation followed by wheat germ agglutinin column chromatography
and anti-CD44-mediated immunoprecipitation indicate that both CD44s and
p185HER2 are expressed on the cell surface and most
importantly, that these two molecules are physically linked to each
other via interchain disulfide bonds. We have also determined that
hyaluronic acid stimulates CD44s-associated p185HER2 tyrosine
kinase activity, leading to an increase in the ovarian carcinoma cell
growth.
After transfection of the ovarian carcinoma cell line with the
adenovirus 5 E1A gene, which is known to repress
p185HER2 expression, we observed that both surface CD44s
expression and CD44s-mediated cell adhesion to hyaluronic acid are
significantly reduced in the transfectant cells compared with the
control cells. These data suggest that down-regulation of
p185HER2 blocks CD44s expression and subsequent adhesion
function. Our findings also indicate that the CD44s-p185HER2
interaction is both functionally coupled and biosynthetically regulated. We believe that direct "cross-talk" between these two surface molecules (i.e. CD44s and the p185HER2) may
be one of the most important signaling events in human ovarian carcinoma development.
Volume 272, Number 44,
Issue of October 31, 1997
pp. 27913-27918
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Interaction between the Adhesion Receptor, CD44, and the Oncogene
Product, p185HER2, Promotes Human Ovarian Tumor Cell
Activation
,
,
,
,
Department of Cell Biology and Anatomy,
School of Medicine, University of Miami, Miami, Florida 33101 and
¶ Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
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