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 chromosome 11 reduces the metastatic capacity of MDA-MB-435 (435) human breast carcinoma cells by 70-90% without affecting tumorigenicity, suggesting the presence of one or more metastasis suppressor genes encoded on human chromosome 11. To identify the gene(s) responsible, differential display comparing chromosome 11-containing (neo11/ 435) and parental, metastatic cells was done. We describe the isolation and functional characterization of a full-length cDNA for one of the novel genes, designated breast-cancer metastasis suppressor 1 (BRMS1), which maps to human chromosome 11q13.1-q13.2. Stably transfected MDA-MB-435 and MDA-MB-231 breast carcinoma cells still form progressively growing, locally invasive tumors when injected into mammary fat pads but are significantly less metastatic to lungs and regional lymph nodes. These data provide compelling functional evidence that breast-cancer metastasis suppressor 1 is a novel mediator of metastasis suppression in human breast carcinoma.
Seraj
M J
MJ
Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey 17033-2390, USA.
Samant
R S
RS
Verderame
M F
MF
Welch
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D009368:Neoplasm Transplantation; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013489:Suppression, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
C410024:BRMS1 protein, human; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D011506:Proteins; D012097:Repressor Proteins