Stable overexpression of MEN1 suppresses tumorigenicity of RAS.
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.
Kim
Y S
YS
Metabolic Diseases Branch, NIDDK, Bethesda, Maryland, MD 20892, USA.
Burns
A L
AL
Goldsmith
P K
PK
Heppner
C
C
Park
S Y
SY
Chandrasekharappa
S C
SC
Collins
F S
FS
Spiegel
A M
AM
Marx
S J
SJ
D016475:3T3 Cells; D000362:Agar; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003470:Culture Media; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D014162:Transfection; D018631:ras Proteins / Q000235:genetics*
D003470:Culture Media; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000362:Agar; D018631:ras Proteins