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A Neu differentiation factor (NDF) domain essential for proliferation and alterations in morphology of colonic
J S Whoriskey1, S K Pekar, G S Elliott
1Amgen Inc., Thousand Oaks, CA 91320, USA.
Abstract:
The Neu Differentiation Factors (NDFs, also termed "heregulins") are a family of proteins that were first isolated as ligands for the HER2 (ergB2, 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 beta 4, was induced in LIM 1215 cells by NDF. These effects were more pronounced with the beta isoform than with the alpha isoform of NDF. The EGF-homology domain of NDF beta was sufficient to stimulate the proliferation and alteration in cell morphology. The use of chemically synthesized chimeric NDF alpha and NDF beta proteins enabled use to identify a region of seven amino acids in the EGF-homology domain of NDF beta that is required for both activities. These in vitro experiments suggest that NDF may act as a regulator of growth and differentiation of colonic epithelial cells in vivo.
Insights
Neu Differentiation Factors (NDFs) stimulate colon cell growth and change their shape. A specific region in NDF beta is key for these effects, suggesting NDFs regulate colon cell development.
Area of Science:
- Cell Biology
- Molecular Biology
- Gastroenterology
Background:
- Neu Differentiation Factors (NDFs), also known as heregulins, are ligands for the HER2 receptor tyrosine kinase.
- The role of NDFs in the regulation of colonic epithelial cells is not fully understood.
Purpose of the Study:
- To investigate the effects of NDFs on colonic epithelial cell proliferation and morphology.
- To identify the specific domains of NDF responsible for these effects.
Main Methods:
- In vitro culture of colonic epithelial cell lines (LIM 1215).
- Treatment with NDF alpha and NDF beta isoforms and chimeric proteins.
- Analysis of cell proliferation, morphology, and protein expression (carcinoembryonic antigen, integrin beta 4).
Main Results:
- NDFs significantly stimulate proliferation and alter the morphology of colonic epithelial cells.
- NDF beta isoform elicits more pronounced effects than NDF alpha.
- A seven-amino acid region within the EGF-homology domain of NDF beta is crucial for its mitogenic and morphogenic activities.
Conclusions:
- NDFs, particularly NDF beta, promote growth and differentiation of colonic epithelial cells in vitro.
- These findings suggest NDFs may play a significant role in regulating colonic epithelial cell behavior in vivo.