Abstract
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.
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Abbreviations
- MEN1:
-
multiple endocrine neoplasia type 1
- MEN1 :
-
gene for MEN1
- WT:
-
wild type
- R:
-
RAS-NIH3T3 cells
- RMX:
-
RAS- and MEN1-transfected NIH3T3 cells, with `X' indicating cell line number(s)
- AEA and SQV:
-
antisera against menin, named by codes for the first three amino acids of the synthetic peptide used for immunization
- G12V:
-
normal glycine at amino acid 12, substituted by valine
- EM:
-
Menin (human sequence with poly-histidine added at N-terminus) expressed in E. coli
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Acknowledgements
We thank Drs Haesook Teresa Kim and David Venzon for statistical analyses. We thank Dr J Sylvio Gutkind for reagents and advice.
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Kim, Y., Burns, A., Goldsmith, P. et al. Stable overexpression of MEN1 suppresses tumorigenicity of RAS. Oncogene 18, 5936–5942 (1999). https://doi.org/10.1038/sj.onc.1203005
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DOI: https://doi.org/10.1038/sj.onc.1203005
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