The APC tumor suppressor is required for epithelial integrity in the mouse mammary gland

Jenifer R. Prosperi, Kimberly R. Becher, Tara A. Willson, Margaret H. Collins, David P. Witte, Kathleen H. Goss

Research output: Contribution to journalArticle

17 Scopus citations


Inactivation of the adenomatous polyposis coli (APC) tumor suppressor has been associated with mammary tumorigenesis in mouse models and through epidemiological studies of human breast cancers, but the normal role for APC in mammary development has not been thoroughly characterized.Wereport here that ApcMin/+ mice containing one functional allele of Apc have severely disrupted lobuloalveolar development during pregnancy and lactation, time points at which Apc gene expression is at its highest levels in normal mice. This phenotype was accompanied by altered proliferation during pregnancy and involution, increased apoptosis throughout lactation, the formation of preneoplastic lesions and changes in specific genes associated with each of these processes. Neither modifications in b-catenin localization, nor the expression of β-catenin transcriptional target genes, were observed in ApcMin/+ mammary tissues; however, tissues from lactating Apc Min/+ mice had a significantly altered epithelial architecture, including disrupted localization of junctional proteins and polarization. Consistent with these findings, APC knockdown in non-transformed mouse mammary epithelial cells in vitro resulted in altered monolayer formation and proliferation without changes in β-catenin-mediated transcription. These results suggest that APC expression is tightly regulated during mammary gland development and is required for normal mammary homeostasis and tumor suppression primarily through maintaining epithelial integrity.

Original languageEnglish (US)
Pages (from-to)319-331
Number of pages13
JournalJournal of cellular physiology
Issue number2
StatePublished - Aug 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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