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Diethylstilbestrol effects and lymphomagenesis in Mlh1 ‐deficient mice
Author(s) -
Kabbarah Omar,
Sotelo Andrea K.,
Mallon Mary Ann,
Winkeler Erin L.,
Fan MingYu,
Pfeifer John D.,
Shibata Darryl,
Gutmann David H.,
Goodfellow Paul J.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20918
Subject(s) - mlh1 , msh2 , dna mismatch repair , cancer research , biology , carcinoma , lymphoma , endometrial cancer , medicine , immunology , cancer , dna repair , genetics , gene
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 C57BL/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. © 2005 Wiley‐Liss, Inc.