Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Mdm2 haplo-insufficiency profoundly inhibits myc-induced lymphomagenesis

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Alt, J. R.
  • Greiner, T. C.
  • Cleveland, John
  • Eischen, C. M.

publication date

  • March 2003

journal

  • EMBO Journal  Journal

abstract

  • Mdm2 harnesses the p53 tumor suppressor, yet loss of one Mdm2 allele in Mdm2(+/-) mice has heretofore not been shown to impair tumor development. Here we report that Mdm2 haplo-insufficiency profoundly suppresses lymphomagenesis in E micro -myc transgenic mice. Mdm2(+/-)E micro -myc transgenics had greatly protracted rates of B cell lymphoma development with life spans twice that of wild-type transgenic littermates. Im paired lymphoma development was associated with drastic reductions in peripheral B cell numbers in Mdm2(+/-)E micro -myc transgenics, and primary pre-B cells from Mdm2(+/-)E micro -myc transgenics and Mdm2(+/-) littermates were extremely susceptible to spontaneous apoptosis. Loss of p53 rescued all of the effects of Mdm2 haplo-insufficiency, indicating they were p53 dependent. Furthermore, half of the lymphomas that ultimately emerged in Mdm2(+/-)E micro -myc transgenics harbored inactivating mutations in p53, and the majority overcame haplo-insufficiency by overexpressing Mdm2. These results support the concept that Mdm2 functions are rate limiting in lymphomagenesis and that targeting Mdm2 will enhance p53-mediated apoptosis, compromising tumor development and/or maintenance.

subject areas

  • Animals
  • Apoptosis
  • B-Lymphocytes
  • Cell Survival
  • Cells, Cultured
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Genes, myc
  • Genes, p53
  • Longevity
  • Lymphoma, B-Cell
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-mdm2
scroll to property group menus

Research

keywords

  • Mdm2
  • Myc
  • apoptosis
  • lymphoma
  • p53
scroll to property group menus

Identity

PubMed Central ID

  • PMC151074

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1093/emboj/cdg133

PubMed ID

  • 12628936
scroll to property group menus

Additional Document Info

start page

  • 1442

end page

  • 1450

volume

  • 22

issue

  • 6

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support