Regulatory Pathways Involved in Heregulin-Induced Proliferation and Differentiation of Human Breast Cancer Cells
Abstract
The polypeptide heregulin has been shown to reverse the transformed phenotype of certain cultured breast cancer cell lines and convert them to more normal, milk-producing cells. In contrast, heregulin has been reported to induce proliferation of other breast cancer cell lines. These diverse effects of heregulin are mediated by receptors in the ErbB/HER family, which function as coreceptor complexes. We first attempted to determine how the different signaling pathways activated by ErbB family receptors could elicit alternatively the differentiation or proliferation of breast cancer cells. These experiments were thwarted by an inability of cultured cell models to consistently show heregulin-induced differentiation. Subsequently, we addressed the mechanism of activation of mitogen-activated protein kinase (MAPK) by heregulin coreceptors in breast cancer cells. Interestingly, we observed that inhibitors of the phosphoinositide (PI) 3-kinase signaling pathway blocked the nuclear translocation of MAPK. These findings indicated a point of significant cross-talk between two major signaling pathways activated by heregulin receptors. In our most recent experiments, we examined the dynamics of the ErbB1 (EGF receptor) C-terminal domain, by generating fluorescently labeled EGF receptor proteins. Time-resolved fluorescence anisotropy measurements indicated that the C-terminal domain exhibited significant mobility on the nanosecond time-scale.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425907
Entities
People
- John Koland
- Nam Lee
Organizations
- University of Iowa