The Physiology of Growth Hormone-Releasing Hormone (GHRH) in Breast Cancer
Abstract
We hypothesize that GHRH functions as an autocrine/paracrine growth factor in neoplastic breast tissue. To address this hypothesis, we are undertaking a comprehensive examination of the physiology of GHRH in immortalized breast cancer cell lines. We report here the results of the first 12 months of this project. The data summarized here indicate that antagonism of the endogenous GHRH autocrine/paracrine system in MDA231 breast cancer cells leads to inhibition of cell proliferation, as well as increased cellular apoptosis, the combination of which leads to decreased cell number. The effect of GHRH antagonism is dose-dependent, transient, and reversible. Furthermore, the results begin to clarify the intracellular pathways involved in the physiology of GHRH in breast cancer cells, implicating P38 kinase and Jun kinase 2, pathways known to be associated with cell proliferation and apoptosis in other tissues. These results are consistent with previous demonstrations of an inhibitory effect of GHRH antagonists on a variety of tumors. Moreover, the results provide initial information regarding the mechanism of action of endogenous GHRH. Continued study of this system should further illuminate the physiology of GHRH in neoplastic tissue, as well as clarifying the therapeutic potential of GHRH receptor antagonists in human neoplasia.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA396630
Entities
People
- Philip S. Zeitler
Organizations
- University of Colorado Health