Assessment of the Tendency of SERMS (Tamoxifen and Raloxifene) to Induce a Metastatic Phenotype in Breast Cancer in a Chemopreventive Setting

摘要

The overall goal of this research is to determine whether the selective estrogen receptor modulator (SERM), tamoxifen can induce a metastatic phenotype in non-invasive estrogen receptor positive (ER+) MCF-7 cells grown as orthotopic xenografts in nude mice. The experiments in this proposal were designed to compare the spread of MCF-7 with that of a well characterized estrogen receptor negative metastatic cell line MDA-MB0- 345 tagged with green fluorescent protein. Pilot studies have shown that tamoxifen can induce the metastatic spread of MCF-7 at least as far as the lymph nodes. Due to morbidity problems unrelated to tumor progression, the major experiment was stopped before it was possible to establish whether MCF-7 can also metastasize to other more distant organs such as the ling, and liver as is seen with the MDA-MD-435 cells. These data suggest that tamoxifen can induce lymphatic spread of non-invasive cell line and promotes the survival of the tumor cells in the lymphatic system. We have not yet established whether hematogenous spread of the ER+ cells can also occur.