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Biology of Somatostatin and Somatostatin Receptors in Breast Cancer.

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Annual rept. 12 Aug 96-11 Aug 97

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The longterm goal of our work is to elucidate the pattern of expression of the five somatostatin receptor SSTR1-5 isoforms in breast cancer, to determine which SSTR subtypes and signalling mechanisms mediate the antiproliferative effects of somatostatin SST, whether the available SST analogs are effective in binding to these antiproliferative SSTR subtypes, and whether the pattern of SSTR expression in tumors can provide an independent prognostic marker. Towards these goals, we have characterized the pattern of expression and relative abundance of mRNA and proteins for SSTR1-5 in 101 primary breast cancers. All tumors expressed at least one SSTR and the majority expressed multiple SSTRs including subtypes 2, 3, and 5 which bind to octapeptide SST analogs. A good correlation was found between SSTR protein expression by immunocytochemistry and mRNA analysis by RT-PCR. SSTRs exert significant antitumor activity both by cytostatic and cytotoxic apoptotic actions in breast cancer cells. Apoptosis is dependent on estrogen receptor expression and is potentiated by tamoxifen. Apoptosis is induced uniquely via the SSTR subtype and is associated with induction of wild type p53 and of Bax and endonuclease 2. By contrast, the other four SSTR subtypes signal cell cycle arrest with the following rank order - SSTR5 SSTR2 SSTR4 SSTR1. These changes are associated with the induction of the retinoblastoma protein pRB and the cyclin-dependent kinase inhibitor p21.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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