Signaling Components of the Anti-Tumor Hormone Somatostatin in Breast Cancer Cells
Annual rept. 22 Sep 1998-21 Sep 1999
COLORADO UNIV HEALTH SCIENCES CENTER DENVER
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The neuropeptide somatostatin is an important regulatory hormone that is widely distributed throughout the body. Somatostatins 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 mechanisms by which somatostatin acts to control breast cancer cell growth remain largely unknown. In this annual progress report, I describe studies performed on MDA23l cells, which show a robust response to somatostatin with regard to growth factor stimulation of the mitogen activated protein kinase, ERK12 or MAPK. The activity of downstream components of the rasrafMAPK pathway, the Ets transcription factors, Ets- 1 and Elk- 1 are also inhibited by somatostatin. Furthermore, I show preliminary 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 somatostatins ability to inhibit cell growth and induce apoptosis in breast cancer. Furthermore, identification of these target pathways defines functional assays by which the efficacy of future anti-cancer drugs can be tested.
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