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Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13
M J Seraj1, R S Samant, M F Verderame
1Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey 17033-2390, USA.
Abstract:
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.
Insights
A novel gene, breast-cancer metastasis suppressor 1 (BRMS1), identified on human chromosome 11, significantly reduces breast cancer metastasis. This discovery offers new insights into controlling cancer spread without affecting tumor growth.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Human chromosome 11 introduction reduced MDA-MB-435 breast carcinoma cell metastasis by 70-90%.
- This suggests metastasis suppressor genes are located on chromosome 11.
Purpose of the Study:
- To identify genes responsible for metastasis suppression on human chromosome 11.
- To isolate and functionally characterize novel metastasis suppressor genes.
Main Methods:
- Differential display was used to compare gene expression between chromosome 11-containing and parental metastatic cells.
- Isolation and functional characterization of a full-length cDNA for a novel gene, breast-cancer metastasis suppressor 1 (BRMS1).
Main Results:
- BRMS1 was identified and mapped to human chromosome 11q13.1-q13.2.
- Stably transfected breast carcinoma cells (MDA-MB-435 and MDA-MB-231) expressing BRMS1 showed significantly reduced metastasis to lungs and lymph nodes.
- Tumorigenicity and local invasiveness remained unaffected.
Conclusions:
- Breast-cancer metastasis suppressor 1 (BRMS1) is a novel mediator of metastasis suppression in human breast carcinoma.
- BRMS1 functions to inhibit cancer cell spread without impacting primary tumor growth.