A Neu Differentiation Factor (NDF) Domain Essential for Proliferation and Alterations in Morphology of Colonic Epithelial CellsIn Vitro

The Neu Differentiation Factors (NDFs, also termed “heregulins”) are a family of proteins that were first isolated as ligands for the HER2 (erbB2, or p185neu) receptor protein tyrosine kinase. Here we show that NDF acts to stimulate the proliferation and alter the cellular morphology of colonic epithelial cells in culture. Dramatic NDF-induced changes in cellular morphology were noted in the colonic epithelial cell line, LIM 1215. In addition, the expression of specific cell proteins, such as carcinoembryonic antigen and integrin β4, was induced in LIM 1215 cells by NDF. These effects were more pronounced with the β isoform than with the a isoform of NDF. The EGF-homology domain of NDFβ was sufficient to stimulate the proliferation and alteration in cell morphology. The use of chemically synthesized chimeric NDFα and NDFβ proteins enabled us to identify a region of seven amino acids in the EGF-homology domain of NDFβ that is required for both activities. These in vitro experiments suggest that NDF may act...