Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer

S. Haricharan, S. M. Hein, J. Dong, M. J. Toneff, O. H. Aina, P. H. Rao, Robert Cardiff, Y. Li

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy or up to 5 years following parturition, and are usually high-grade, connective tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is known about the cellular origin of PABCs or the mechanisms by which PABCs are initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previously reported MMTV-tva transgenic mice, we detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors during pregnancy and lactation. These high-grade and stroma-rich tumors were less frequent in involuted mice or in age-matched nulliparous mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP+ mammary alveolar cells, we found that tumors had similar morphological phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative), irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC.

Original languageEnglish (US)
Pages (from-to)5729-5739
Number of pages11
JournalOncogene
Volume33
Issue number50
DOIs
StatePublished - Dec 11 2014

Keywords

  • alveolar cells
  • breast cancer
  • PABC
  • pregnancy

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Haricharan, S., Hein, S. M., Dong, J., Toneff, M. J., Aina, O. H., Rao, P. H., Cardiff, R., & Li, Y. (2014). Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer. Oncogene, 33(50), 5729-5739. https://doi.org/10.1038/onc.2013.521