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PMID: 9553042 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors.

Genes & development ·Vol. 12 ·No. 8 ·1998-04-15 ·Pages 1121-33

McClatchey AI, Saotome I, Mercer K, Crowley D, Gusella JF, Bronson RT, Jacks T

Abstract

A role for the membrane/cytoskeleton interface in the development and progression of cancer is established, yet poorly understood. The neurofibromatosis type II (NF2) tumor suppressor gene encodes a member of the ezrin/radixin/moesin (ERM) family of membrane/cytoskeleton linker proteins thought to be important for cell adhesion and motility. We report that in contrast to the narrow spectrum of benign tumors in human NF2 patients, Nf2 heterozygous mice develop a variety of malignant tumors. Using the fact that Nf2 is linked to the p53 tumor suppressor locus in the mouse we have also investigated the effects of genetic linkage of cancer-predisposing mutations on tumorigenesis and examined the genetic pathway to tumor formation involving Nf2 loss. Importantly, we observed a very high rate of metastasis associated with Nf2 deficiency, with or without loss of p53 function, and we provide experimental evidence supporting a role for Nf2 loss in metastatic potential. Together, our results suggest an important role for the NF2 tumor suppressor, and perhaps the ERM family in tumor formation and metastasis.

MeSH Terms
Animals Female Genes, Neurofibromatosis 2 Genes, p53 Heterozygote Humans Male Membrane Proteins/genetics,physiology Mice Mice, Inbred C57BL Mutagenesis Neoplasm Proteins/genetics,physiology Neoplasms, Experimental/genetics,physiopathology,secondary Neurofibromin 2 Tumor Cells, Cultured
Chemicals
Membrane Proteins Neoplasm Proteins Neurofibromin 2
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
McClatchey A I
Department of Biology and the Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. [email protected]
Saotome I
Mercer K
Crowley D
Gusella J F
Bronson R T
Jacks T
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.12.8.1121
Email
[email protected]
Published
1998-04-15
Pages
1121-33
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316711
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.12.8.1121 PMC Full Text View journal details
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