c-erbB-2 (HER-2/neu) gene amplification is a better indicator of poor prognosis than protein over-expression in operable breast-cancer patients

Abstract

We investigated the effect of hepatocyte‐derived extracellular matrix (ECM) on the expression of erb‐B2 and erb‐B3 in colon cancer cell lines, as well as the role of erb‐B2 and erb‐B3 in colon cancer cell proliferation. Colon cancer cell lines plated on hepatocyte‐derived ECM had increased protein levels of both erb‐B2 and erb‐B3. The addition of soluble recombinant proteoglycan syndecan‐4 also resulted in higher expression of erb‐B2 and erb‐B3. We prepared hepatocyte‐derived ECM from 1 to 7 days' cultures of hepatocytes, which contained different amounts of sulfated glycosaminoglycans. There was a direct correlation between the amounts of sulfated glycosaminoglycans in the ECM and the levels of erb‐B2 and erb‐B3 in the colon cell line KM12. The stimulatory effect of hepatocyte‐derived ECM was abolished when the colon cancer cells were cultured in the presence of antibodies to erb‐B2. These studies show that hepatocyte‐derived ECM and the heparan sulfate proteoglycans present in it are responsible for inducing erb‐B2 and erb‐B3 in colon cancer cells. The growth stimulatory effect of extracellular matrix is mediated, at least in part, by increased expression of erb‐B2 and erb‐B3.