Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice

Winfried Edelmann, Kan Yang, Mari Kuraguchi, Joerg Heyer, Marie Lia, Burkhard Kneitz, Kunhua Fan, Anthony M C Brown, Martin Lipkin, Raju Kucherlapati

Research output: Contribution to journalArticle

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Abstract

MutL homologue 1 (MLH1) is a member of the family of proteins required for DNA mismatch repair. Germ-line mutations in MLH1 lead to the cancer susceptibility syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We generated mice carrying a null mutation in the Mlh1 gene. We showed that mice heterozygous and homozygous for the Mlh1 gene are predisposed to developing tumors of the gastrointestinal (GI) tract, lymphomas, and a number of other tumor types. We also examined the role of adenomatous polyposis coli gene (Apc) gene mutations in the GI tumors of Mlh1 mutant mice by different methods and showed that the GI tumors in Mlh1 mice express little or no adenomatous polyposis coli protein. When an Apc gene mutation was bred into the Mlh1 mutant mice, the GI tumor incidence increased 40-100-fold. The wild- type Apc allele in these tumors was found to contain mutations. Together, these results show that we have developed two mouse models for human HNPCC and that the mechanisms of tumor development in the GI tract of these mice involve loss of Apc gene function in a manner very similar to that seen in the GI tumors of HNPCC.

Original languageEnglish (US)
Pages (from-to)1301-1307
Number of pages7
JournalCancer Research
Volume59
Issue number6
StatePublished - Mar 15 1999

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Carcinogenesis
APC Genes
Hereditary Nonpolyposis Colorectal Neoplasms
Neoplasms
Mutation
Genes
Gastrointestinal Tract
Adenomatous Polyposis Coli Protein
DNA Mismatch Repair
Germ-Line Mutation
Lymphoma
Alleles
Incidence
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Edelmann, W., Yang, K., Kuraguchi, M., Heyer, J., Lia, M., Kneitz, B., ... Kucherlapati, R. (1999). Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Research, 59(6), 1301-1307.

Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. / Edelmann, Winfried; Yang, Kan; Kuraguchi, Mari; Heyer, Joerg; Lia, Marie; Kneitz, Burkhard; Fan, Kunhua; Brown, Anthony M C; Lipkin, Martin; Kucherlapati, Raju.

In: Cancer Research, Vol. 59, No. 6, 15.03.1999, p. 1301-1307.

Research output: Contribution to journalArticle

Edelmann, W, Yang, K, Kuraguchi, M, Heyer, J, Lia, M, Kneitz, B, Fan, K, Brown, AMC, Lipkin, M & Kucherlapati, R 1999, 'Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice', Cancer Research, vol. 59, no. 6, pp. 1301-1307.
Edelmann W, Yang K, Kuraguchi M, Heyer J, Lia M, Kneitz B et al. Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Research. 1999 Mar 15;59(6):1301-1307.
Edelmann, Winfried ; Yang, Kan ; Kuraguchi, Mari ; Heyer, Joerg ; Lia, Marie ; Kneitz, Burkhard ; Fan, Kunhua ; Brown, Anthony M C ; Lipkin, Martin ; Kucherlapati, Raju. / Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. In: Cancer Research. 1999 ; Vol. 59, No. 6. pp. 1301-1307.
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