agar and Multiple-Endocrine-Neoplasia-Type-1

Although there is indirect genetic evidence that MEN1, the gene for multiple endocrine neoplasia type 1, is a tumor suppressor gene, little is known about the MEN1-encoded protein, menin. Menin was stably overexpressed in a well-characterized murine tumor cell line, (valine-12)-RAS-transformed NIH3T3 cells. Menin overexpression reverted the morphology of the RAS-transformed NIH3T3 cells towards the more flattened and more spread, fibroblastic shape of wild type NIH3T3 cells. The proliferation rate of the RAS-transformed cells in 0.5% calf serum was also slower with menin overexpression. Menin overexpression reduced the RAS-induced clonogenicity in soft agar. Menin also reduced tumor growth after injection of cells in nude mice. In conclusion, stable overexpression of MEN1 suppressed partially the RAS-mediated tumor phenotype in vitro and in vivo. Overexpressed menin protein had biological effects, directly supporting MEN1 gene function as a tumor suppressor.

Topics: 3T3 Cells; Agar; Amino Acid Sequence; Animals; Cell Division; Cell Nucleus; Cell Transformation, Neoplastic; Cells, Cultured; Culture Media; Fibroblasts; Gene Expression Regulation; Genes, Tumor Suppressor; Humans; Mice; Mice, Nude; Molecular Sequence Data; Multiple Endocrine Neoplasia Type 1; Neoplasm Proteins; Proto-Oncogene Proteins; ras Proteins; Transfection