Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13

We previously showed that introduction of a normal, neomycin-tagged human c hromosome 11 reduces the metastatic capacity of MDA-MB-435 (435) human brea st carcinoma cells by 70-90% without affecting tumorigenicity, suggesting t he presence of one or more metastasis suppressor genes encoded on human chr omosome ii. To identify the gene(s) responsible, differential display compa ring chromosome 11-containing (neo11/435) and parental, metastatic cells wa s done. We describe the isolation and functional characterization of a full -length cDNA for one of the novel genes, designated breast-cancer metastasi s suppressor 1 (BRMS1), which maps to human chromosome 11q13.1-q13.2. Stabl y transfected MDA-MB-435 and MDA-MB-231 breast carcinoma cells still form p rogressively growing, locally invasive tumors when injected into mammary fa t pads but are significantly less metastatic to lungs and regional lymph no des. These data provide compelling functional evidence that breast-cancer m etastasis suppressor 1 is a novel mediator of metastasis suppression in hum an breast carcinoma.