Diethylstilbestrol effects and lymphomagenesis in Mlh1-deficient mice

Omar Kabbarah, Andrea K. Sotelo, Mary Ann Mallon, Erin L. Winkeler, Ming Yu Fan, John D. Pfeifer, Darryl Shibata, David H. Gutmann, Paul J. Goodfellow

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10 Scopus citations

Abstract

Inherited defects in DNA mismatch repair (MMR) predispose to a variety of malignancies in humans and in mouse knockout models. In humans, hemizygosity for one of several DNA MMR genes greatly increases an individual's risk for colon and endometrial carcinoma. Hemizygous mice develop gastrointestinal tumors at a low to moderate frequency. Homozygous nulls have higher rates of gastrointestinal tumors and are particularly susceptible to lymphoma. In an effort to model endometrial carcinoma associated with mutation in MMR, we treated mice carrying knockout alleles for Mlh1 or Msh2 with the synthetic estrogen diethylstilbestrol (DES), a known promoter of uterine endometrial carcinoma. The CS7BL/6 mice carrying DNA MMR mutations failed to develop endometrial carcinomas. However, the Mlh1-deficient mice treated with DES tended to become moribund at an early age and had very early onset of lymphoma. Comparison of DES-treated and untreated Mlh1-/- animals suggests the combination of Mlh1 deficiency and DES exposure accelerates lymphomagenesis.

Original languageEnglish
Pages (from-to)666-669
Number of pages4
JournalInternational Journal of Cancer
Volume115
Issue number4
DOIs
StatePublished - Jul 1 2005

Keywords

  • DNA mismatch repair
  • Diethylstilbestrol
  • Hereditary nonpolyposis colorectal cancer
  • MLH1
  • MSH2
  • MutL homologue 1
  • MutS homologue 2

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    Kabbarah, O., Sotelo, A. K., Mallon, M. A., Winkeler, E. L., Fan, M. Y., Pfeifer, J. D., Shibata, D., Gutmann, D. H., & Goodfellow, P. J. (2005). Diethylstilbestrol effects and lymphomagenesis in Mlh1-deficient mice. International Journal of Cancer, 115(4), 666-669. https://doi.org/10.1002/ijc.20918