Regulatory Pathways Involved in Heregulin-Induced Proliferation and Differentiation of Human Breast Cancer Cells
Abstract
The polypeptide heregulin is involved in normal mammary development and controls the proliferation of human breast cancer cells. These effects of heregulin are mediated by receptors in the ErbB/HER family. How ErbB family receptors function to control breast cancer cell proliferation was investigated in the previous year. Our research elaborated upon our discovery of a cross-communication between two distinct signaling pathways activated by heregulin receptors. Specifically, we had observed that the phosphoinositide (PT) 3-kinase signaling pathway was necessary for mitogen-activated protein kinase (MAPK) signaling, i.e., the appearance of activated MAPK in the cell nucleus. This novel effect whereby two well-studied growth-promoting pathways cooperate in signaling to the nucleus could be of major significance in breast cancer growth control. Two crucial questions about this signaling interaction were addressed: (1) whether the involvement of PT 3-kinase in MAPK activation could be observed in a cell line not of breast cancer origin, and (2) at which step of the MAPK signaling cascade was PT 3-kinase signaling involved. We determined that the affect of PT 3-kinase occurred in a non-transformed fibroblast cell line, and that the involvement of PT 3-kinase was subsequent to MAPK activation, possibly in the MAPK nuclear translocation event itself.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADA391956
Entities
People
- Huaming Tan
- John Koland
Organizations
- University of Iowa