Date of Award

6-1999

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Michael McLeod

Second Advisor

Dr. Bruce Bejcek

Third Advisor

Dr. Dave Reinhold

Fourth Advisor

Dr. John Spitsbergen

Access Setting

Masters Thesis-Open Access

Abstract

The hormone Somatostatin (SMS) and its analogs have been shown to mediate a variety of cellular actions including inhibition of cellular growth and differentiation of endocrine tumors such as insulinomas and glucagonomas. The mechanisms by which SMS exerts its antitumorigenic effects are poorly understood but are thought to include one of the five Somatostatin receptors (SSTR1-5), and the protein tyrosine phosphatase SHP-1. To determine if the antiproliferative effects of SMS were due to the presence of the SSTR2 receptor or the stimulation of SHP-1, we introduced cDNA's of the SMS receptor SSTR2, SHP-1, and a dominant negative mutant of SHP-1 into NIH-3T3 cells by lipofection. Our research has shown that the expression of the SSTR2 receptor and the SHP-1 gene product controls cellular proliferation. We have also shown that both the SSTR2 receptor and the SHP-1 gene product can control activation of MAPK proteins. Our results also demonstrate that the SMS analog Sandostatin can control MAPK activation in cells that express the SSTR2 receptor. We therefore conclude that SMS and its analog Sandostatin have different modes of action within the NIH-3T3 mouse fibroblast cell line.

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