Overexpression of activated murine notch1 and notch3 in transgenic mice blocks mammary gland development and induces mammary tumors

Hu Chunyan, Dievart Anne, Lupien Mathieu, Calvo Ezequiel, Tremblay Gilles, Jolicoeur Paul. 2006. Overexpression of activated murine notch1 and notch3 in transgenic mice blocks mammary gland development and induces mammary tumors. American Journal of Pathology, 168 (3) : pp. 973-990.

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Liste HCERES des revues (en SHS) : oui

Thème(s) HCERES des revues (en SHS) : Psychologie-éthologie-ergonomie

Abstract : The mouse mammary tumor virus (MMTV) provirus was found to target the Notch1 gene, producing insertional mutations in mammary tumors of MMTV/neu transgenic (Tg) mice. In these mammary tumors, the Notch1 gene is truncated upstream of the transmembrane domain, and the resulting Notch1 intracellular domain (Notch1(intra)), deleted of most extracellular sequences, is overexpressed. Although Notch1(intra) transforms mammary epithelial cells in vitro, its role in mammary gland tumor formation in vivo was not studied. Therefore, we generated MMTV/Notch1(intra) Tg mice that overexpress murine Notch1(intra) in the mammary glands. We observed that MMTV/Notch1(intra) Tg females were unable to feed their pups because of impaired ductal and lobulo-alveolar mammary gland development. This was associated with decreased proliferation of ductal and alveolar epithelial cells during rapid expansion at puberty and in early pregnancy, as well as decreased production of beta-casein. Notch1(intra) repressed expression of the beta-casein gene promoter, as assessed in vitro with a beta-casein/luciferase reporter construct. The MMTV/Notch1(intra) Tg females developed mammary gland tumors, confirming the oncogenic potential of Notch1(intra) in vivo. Furthermore, MMTV/Notch3(intra) Tg mice exhibited a very similar phenotype. Thus, these Tg mice represent novel models for studying the role of Notch1 or Notch3 in the development and transformation of the mammary gland. (Résumé d'auteur)

Classification Agris : L73 - Animal diseases
L10 - Animal genetics and breeding
L52 - Animal physiology - Growth and development

Champ stratégique Cirad : Axe 4 (2005-2013) - Santé animale et maladies émergentes

Auteurs et affiliations

  • Hu Chunyan, Clinical Research Institute of Montréal (CAN)
  • Dievart Anne, Clinical Research Institute of Montréal (CAN) ORCID: 0000-0001-9460-4638
  • Lupien Mathieu, Clinical Research Institute of Montréal (CAN)
  • Calvo Ezequiel, Clinical Research Institute of Montréal (CAN)
  • Tremblay Gilles, McGill University (CAN)
  • Jolicoeur Paul, Université de Montréal (CAN)

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