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Breast cancer metastasis-suppressor gene identified
Cure rates for breast cancer drop significantly when tumour cells disseminate and colonise distant sites, and so decreased morbidity and mortality from this disease will depend on the effective treatment of metastasis. This possibility came a step closer to realisation recently as researchers at Pennsylvania State University published evidence that they have identified a gene responsible for suppressing metastasis of breast cancer [1]. Dr Danny Welch and colleagues successfully isolated and functionally characterised the metastasis suppressor gene, designated BRMS1 (Accession no. AF159141, GenBank), and found that the gene maps to a 'hot-spot' in breast cancer progression, human chromosome 11q13.
Welch and co-workers previously found that metastasis was suppressed by 70-90% when a normal human chromosome 11 was introduced into metastatic MDA-MB-435 (435) human breast carcinoma cells, with no affect on tumorigenicity. In their latest study, they tested the hypothesis that chromosome 11q encodes a metastasis suppressor gene and set out to identify the gene responsible.
They did this using differential display technology to compare mRNA expression of parental metastatic and non-metastatic 435 breast carcinoma cells following the introduction of chromosome 11. The differentially expressed gene, BRMS1, was then isolated using RTPCR, cloned and mapped to human chromosome 11q13.1-q13.2 using fluorescent in situ hybridisation techniques. They then stably transfected breast cancer cell lines and injected these transformants into the mammary fat pads of mice. A comparison of the transfected mice and the control groups showed that the growth rate of tumours was similar in both groups, but the incidence and number of metastases in the lung and regional lymph nodes were significantly suppressed in the BRMS1 transfectants compared with the vector only controls. The authors state: "Taken together, these data fulfil the functional definition that BRMS1 is a metastatic-suppressor gene, i.e. metastases is suppressed whereas tumorigenicity is not".
The authors conclude that the mechanism by which BRMS1 suppresses metastasis is yet to be fully determined, but an understanding of BRMS1 function may help prevent breast cancer cells from colonising distant sites and improve breast cancer survival.
1Seraj MJ, Samant RS, Verderame MF, Welch DR. Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13.
Cancer Res 2000, 60, 2764-2769.
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