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The leading cause of morbidity and mortality of breast cancer patients is metastasis. BRMS1 suppresses metastasis without blocking tumorigenesis in multiple human and murine cancer cells of diverse origins. However, the molecular mechanisms of BRMS1 are not well understood. Interestingly, several databases include mRNA and EST sequences suspected of being alternatively spliced variants of BRMS1. To test whether splice variants exist in human cell lines and function in the progression of breast cancer, we designed primers specific to several of the putative variants. The genetically related cell lines representing premalignant breast disease (MCF10A and MCF10AT) and metastatic carcinoma (MCF10CA a.1 and MCF10CA d.1α) were probed by RT-PCR and found to express three additional BRMS1variants [NM_001024957 (BRMS1.v2), NM_001024958 (BRMS1.v3) and BRMS1.v4, which does not yet have an accession number]. Significantly, BRMS1.v2 and BRMS1.v4 are only detected in the premalignant MCF10A and AT cell lines, while BRMS1and BRMS1.v3 were detected in all four lines. Differential expression of alternatively spliced variants of BRMS1in premalignant versus metastatic cells suggests that: 1) only select variants are involved in metastasis regulation, 2) specific variants are responsible for the pathogenesis of breast carcinoma, and 3) certain variants could be exploited for prognostic and/or therapeutic purposes. Support: CA87728, F32CA113037, CA89019, and National Foundation for Cancer Research

[Proc Amer Assoc Cancer Res, Volume 47, 2006]