Neu Differentiation Factor (Heregulin) Induces Expression of Intercellular Adhesion Molecule 1: Implications for Mammary Tumors

摘要: Neu differentiation factor (NDF, also called heregulin) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation of the Neu/HER-2 receptor and induces phenotypic certain mammary cancer cell lines to growth-arrested milk-producing cells. To determine which molecules participate in concomitant morphological alterations, we analyzed expression several cytoskeletal surface found NDF elevated intercellular adhesion molecule 1 (ICAM-1) cultured AU-565 human adenocarcinoma The levels both protein mRNA ICAM-1 were after 3-5 days treatment with NDF. Elevated was induced by gamma-interferon tumor-promoting phorbol ester (PMA), albeit different kinetics. Down-regulation kinase C or its inhibition calphostin partially inhibited effect NDF, implying induction may be mediated C. transcripts detectable 3 9 tumors, suggesting vitro relevant breast cancer. By selecting Neu-positive tumors (n = 39), significant correlation (P < 0.001) between histological features invasive ductal carcinoma prominent situ component. When cells these grew clusters formed domelike structures reminiscent comedo-type situ. In addition, majority patients coexpressed had no lymph node involvement, unlike most but ICAM-1-negative metastasized lymphatic system. Taken together, our observations suggest affect morphology, state, metastasis Neu-expressing tumor