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2008 Annual Meeting Posters


The Effect of Ras/Raf-1 Pathway Activation On Somatostatin Receptors in Gastrointestinal Carcinoid Tumor Cells
Scott N. Pinchot*, Herbert Chen
Surgery, University of Wisconsin Hospital and Clinics, Madison, WI

Background: Gastrointestinal (GI) carcinoid tumors often cause debilitating symptoms due to excessive hormonal secretion. We have previously shown that activation of the ras/raf-1 signal transduction pathway in GI carcinoids markedly suppresses chromogranin A (CgA) and serotonin production. Since somatostatin agonists have been shown to have similar effects, we hypothesized that raf-1 activation modulates neuroendocrine (NE) hormone production through alterations in somatostatin receptor (SSTR) expression.
Methods: Gastrointestinal carcinoid (BON) cells and an estrogen-inducible raf-1 cell line (BON-raf) were used to study the effects of raf-1 activation on somatostatin receptors (SSTR1-5). Cells were treated with either control (ethanol) or β-estradiol for two days. Protein isolates were analyzed by Western blot to confirm raf-1 activation and determine the level of somatostatin receptor activity utilizing subtype-specific antibodies for SSTR1-5.
Results: Estrogen treatment of BON-raf cells resulted in raf-1 pathway activation. Western blot analysis identified the presence of SSTR 1 and SSTR3-5 subtypes in BON cells; the SSTR2 subtype was not expressed. Raf-1 activation resulted in no significant alterations in SSTR subtype expression.
Conclusions: Raf-1 mediated suppression of CgA and serotonin is not due to alterations in SSTR expression. NE hormonal suppression is therefore effected via an alternative mechanism. However, understanding the regulation of these receptors in response to raf-1 activation is an important first step in studying a potential synergistic effect between raf-1 activating compounds and somatostatin agonists.


 

 
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