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Title: A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation,more » to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.« less
 [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [2] ;  [2] ;  [3] ;  [4] ;  [5] ;  [1] ;  [1]
  1. Univ. de Salamanca/CSIC, Salamanca (Spain); Hospital Univ. de Salamanca, Salamanca (Spain)
  2. Univ. de Salamanca, Salamanca (Spain); Hospital Univ. de Salamanca, Salamanca (Spain)
  3. Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid (Spain)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  5. Maine Medical Center Research Institute, Scarborough, ME (United States)
Publication Date:
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Grant/Contract Number:
Accepted Manuscript
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Additional Journal Information:
Journal Volume: 34; Journal Issue: 36; Journal ID: ISSN 0950-9232
Research Org:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States