Suppression of Human Melanoma Metastasis by the Metastasis Suppressor Gene, BRMS1

We recently identified a novel metastasis suppressor gene, BRMS1, in breast cancer. Since the BRMS1 gene maps to chromosome 11q13.1-q13.2 and since chromosome 11q defects have been described in various stages of human melanoma progression, we hypothesized that BRMS1 may function as a tumor or metast...

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Bibliographic Details
Published in:Experimental cell research 2002-02, Vol.273 (2), p.229-239
Main Authors: Shevde, Lalita A, Samant, Rajeev S, Goldberg, Steven F, Sikaneta, Tabo, Alessandrini, Alessandro, Donahue, Henry J, Mauger, David T, Welch, Danny R
Format: Article
Language:English
Subjects:
Animals
Base Sequence
BRMS1
chromosome 11
Coculture Techniques
Disease Models, Animal
DNA, Complementary
Female
gap junctions
Humans
invasion
Lung Neoplasms - secondary
Melanocytes - metabolism
melanoma
Melanoma, Experimental - pathology
metastasis
Mice
Mice, Nude
Molecular Sequence Data
Neoplasm Metastasis
Neoplasm Proteins
Proteins - genetics
Proteins - physiology
Repressor Proteins
Reverse Transcriptase Polymerase Chain Reaction
suppression
Tumor Cells, Cultured
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Summary:We recently identified a novel metastasis suppressor gene, BRMS1, in breast cancer. Since the BRMS1 gene maps to chromosome 11q13.1-q13.2 and since chromosome 11q defects have been described in various stages of human melanoma progression, we hypothesized that BRMS1 may function as a tumor or metastasis suppressor in melanomas as well. Quantitative real-time RT-PCR revealed that BRMS1 mRNA expression was high in melanocytes, considerably reduced in early melanoma-derived cell lines, and barely detectable in advanced/metastatic cell lines. Stable transfectants of BRMS1 in the human melanoma cell lines MelJuSo and C8161.9 did not alter the tumorigenicity of either cell line, but significantly suppressed metastasis compared to vector-only transfectants. Orthotopic tumors continued to express BRMS1, but expression was lost in lung metastases. In vitro morphology, growth rate, and histology of BRMS1 transfectants were similar to controls. BRMS1 transfectants were less invasive in a collagen sandwich assay and had restored homotypic gap junctional intercellular communication (GJIC). Thus, BRMS1 functions as a metastasis suppressor in more than one tumor type (i.e., breast carcinoma and cutaneous melanoma) by modifying several metastasis-associated phenotypes.
ISSN:0014-4827
1090-2422
DOI:10.1006/excr.2001.5452