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 second 12 months of this project. The data summarized here indicate that endogenous GHRH acts as a growth factor through activation of MAPK/ERK (in a ras and/or raf dependent fashion). In addition, the data suggest an anti-apoptotic action of GHRH through suppression of p38 activation of a caspase cascade (9 succeeds 3 succeeds 2) and consequent inhibition of Bcl-2 cleavage. Activation of an independent Jnk pathway may antagonize the effects of GHRH on the p38 pathway. The emerging picture of the pathway by which GHRH promotes growth and inhibits apoptosis in breast cancer cell lines furthers our understanding of the previously demonstrated actions of GHRH antagonists to inhibit breast cancer growth in vitro and in vivo. More importantly, this understanding begins to suggest ways in which GHRH antagonists might fit into therapeutic regimens, as pro-apoptotic agents in their own right or as adjuvant agents supporting the action of traditional anti-neoplastics.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407126
Entities
People
- Philip S. Zeitler
Organizations
- University of Colorado Health