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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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
Volume220
Issue number2
DOIs
StatePublished - Aug 2009
Externally publishedYes

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Catenins
Adenomatous Polyposis Coli
Human Mammary Glands
Tumors
Breast
Genes
Tissue
Neoplasms
Lactation
Transcription
Gene expression
Monolayers
Breast Neoplasms
Pregnancy
Polarization
Apoptosis
Epidemiologic Studies
Carcinogenesis
Homeostasis
Epithelial Cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

The APC tumor suppressor is required for epithelial integrity in the mouse mammary gland. / Prosperi, Jenifer; Becher, Kimberly R.; Willson, Tara A.; Collins, Margaret H.; Witte, David P.; Goss, Kathleen H.

In: Journal of Cellular Physiology, Vol. 220, No. 2, 08.2009, p. 319-331.

Research output: Contribution to journalArticle

Prosperi, Jenifer ; Becher, Kimberly R. ; Willson, Tara A. ; Collins, Margaret H. ; Witte, David P. ; Goss, Kathleen H. / The APC tumor suppressor is required for epithelial integrity in the mouse mammary gland. In: Journal of Cellular Physiology. 2009 ; Vol. 220, No. 2. pp. 319-331.
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