PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer

Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11405-10. doi: 10.1073/pnas.0911186107. Epub 2010 Jun 4.

Abstract

After lactation, weaning causes mammary epithelial cell (MEC) apoptosis. MECs express the plasma membrane calcium-ATPase 2 (PMCA2), which transports calcium across the apical surface of the cells into milk. Here we show that PMCA2 is down-regulated early in mammary involution associated with changes in MEC shape. We demonstrate that loss of PMCA2 expression raises intracellular calcium levels and sensitizes MECs to apoptosis. In contrast, overexpression of PMCA2 in T47D breast cancer cells lowers intracellular calcium and protects them from apoptosis. Finally, we show that high PMCA2 expression in breast cancers is associated with poor outcome. We conclude that loss of PMCA2 expression at weaning triggers apoptosis by causing cellular calcium crisis. PMCA2 overexpression, on the other hand, may play a role in breast cancer progression by conferring resistance to apoptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Breast Neoplasms / metabolism*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / pathology
  • Mammary Neoplasms, Animal / metabolism*
  • Mice
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Plasma Membrane Calcium-Transporting ATPases / metabolism*
  • RNA, Messenger / metabolism
  • Treatment Outcome

Substances

  • RNA, Messenger
  • Plasma Membrane Calcium-Transporting ATPases
  • ATP2B2 protein, human
  • Atp2b2 protein, mouse

Associated data

  • GENBANK/GU734816