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Advances in Brief |
Ernest Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720
We have previously shown that expression of heregulin (HRG) is closely
correlated with breast cancer progression. We have subsequently
isolated Cyr61, a ligand for the 
vß3
integrin that is differentially expressed in HRG-positive cells, and
have shown that it is expressed in all of the invasive and metastatic
breast cancer cell lines tested. Preliminary evaluation of Cyr61
expression in breast tumor biopsies revealed expression of Cyr61 in
about 30% of invasive breast carcinomas. Significantly, we
demonstrated that Cyr61 is a downstream effector of HRG action, because
a Cyr61-neutralizing antibody abolished the ability of HRG-expressing
cells to migrate in vitro. Furthermore, we have shown
that HRG-expressing cells denote higher levels of
vß3 expression, and we have established
that Cyr61 action is mediated, at least in part, through its receptor
vß3, because a functional blocking
antibody of the vß3 blocked the Matrigel
outgrowth of HRG-expressing cells. These results strongly suggest that
Cyr61 is necessary for HRG-mediated chemomigration and that Cyr61 plays
a functional role in breast cancer progression, possibly through its
interactions with the vß3 receptor.
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