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 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.
Shevde
Lalita A
LA
Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033-2390, USA.
Samant
Rajeev S
RS
Goldberg
Steven F
SF
Sikaneta
Tabo
T
Alessandrini
Alessandro
A
Donahue
Henry J
HJ
Mauger
David T
DT
Welch
Danny R
DR
D000818:Animals; D001483:Base Sequence; D018920:Coculture Techniques; D018076:DNA, Complementary; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D008544:Melanocytes / Q000378:metabolism; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C410024:BRMS1 protein, human; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D011506:Proteins; D012097:Repressor Proteins