Signaling Components of the Anti-Tumor Hormone Somatostatin in Breast Cancer Cells

摘要

The neuropeptide somatostatin is an important regulatory hormone that is widely distributed throughout the body. Somatostatin's actions are primarily inhibitory, and recently, it has been utilized as an antiproliferative agent against several tumor types, including breast neoplasms. Experimentally and clinically, somatostatin can inhibit breast cancer cell growth, possibly by inhibiting the secretion of growth factors, or by acting directly on the cells themselves to induce programmed cell death, or apoptosis. Despite increased clinical use, the mechanism(s) by which somatostatin acts to control breast cancer cell growth remain largely unknown. In this final report, I describe studies performed to survey of numerous breast cancer cell lines to predict their usefulness as models to study somatostatin action, which comprised Aim 1 of the proposal. One cell line, MDA231, shows a robust response to somatostatin with regard to growth factor stimulation of the mitogen activated protein kinase, ERK1/2 (or MAPK). Specifically, the somatostatin analog BIM23014 caused a marked dimunition of EGF-stimulated MAPK activity, likely mediated by the type 2 somatostatin receptor. Furthermore, I show data indicating that another signaling pathway, the jun n-terminal kinase (JNK) pathway may be activated in response to somatostatin. Together, these results begin to explain somatostatin's ability to inhibit cell growth and induce apoptosis in breast cancer. Identification of these target pathways defines functional assays by which the efficacy of future anti-cancer drugs can be tested.