Secretory pathway Ca2+-ATPases promote in vitro microcalcifications in breast cancer cells

Donna Dang, Hari Prasad, Rajini Rao

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Calcification of the breast is often an outward manifestation of underlying molecular changes that drive carcinogenesis. Up to 50% of all non-palpable breast tumors and 90% of ductal carcinoma in situ present with radiographically dense mineralization in mammographic scans. However, surprisingly little is known about the molecular pathways that lead to microcalcifications in the breast. Here, we report on a rapid and quantitative in vitro assay to monitor microcalcifications in breast cancer cell lines, including MCF7, MDA-MB-231, and Hs578T. We show that the Secretory Pathway Ca2+-ATPases SPCA1 and SPCA2 are strongly induced under osteogenic conditions that elicit microcalcifications. SPCA gene expression is significantly elevated in breast cancer subtypes that are associated with microcalcifications. Ectopic expression of SPCA genes drives microcalcifications and is dependent on pumping activity. Conversely, knockdown of SPCA expression significantly attenuates formation of microcalcifications. We propose that high levels of SPCA pumps may initiate mineralization in the secretory pathway by elevating luminal Ca2+. Our new findings offer mechanistic insight and functional implications on a widely observed, yet poorly understood radiographic signature of breast cancer.

Original languageEnglish (US)
Pages (from-to)2474-2485
Number of pages12
JournalMolecular Carcinogenesis
Issue number11
StatePublished - Nov 2017


  • alizarin red
  • biomineralization
  • breast cancer
  • calcium ATPase
  • calcium transport
  • hydroxyapatite
  • microcalcification
  • secretory pathway

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research


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