Does Increased Expression of the Plasma Membrane Calcium-ATPase Isoform 2 Confer Resistance to Apoptosis on Breast Cancer Cells?
Abstract
The plasma membrane calcium ATPase isoform 2 (PMCA2) is highly expressed on the apical membrane of mammary epithelial cells during lactation, and is the predominant pump responsible for calcium transport into milk. The lack of PMCA2 causes a low epithelial content in pregnant deafwaddler (dfw 2J) mouse mammary glands due to widespread apoptosis. The apoptosis is likely a result of elevated cytosolic calcium levels due an imbalance of calcium influx and efflux, suggesting that PMCA2 is important not only for calcium transport into milk, but also for maintaining cytosolic calcium levels. In addition, PMCA2 expression correlates with tumor grade, metastases, estrogen receptor negativity, docetaxol resistance, and poor 5 year survival in human breast cancer. We hypothesize that overexpression of PMCA2 and subsequent enhanced intracellular calcium clearance is a mechanism by which breast cancer cells escape apoptosis. The aims of this research are to determine whether PMCA2 expression correlates with cytosolic calcium levels and sensitivity to apoptosis in human breast cancer cells lines, and whether the absence of PMCA2 alters tumorigenesis or induces drug resistance in a transgenic model of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2008
- Accession Number
- ADA493700
Entities
People
- Joshua N. Vanhouten
Organizations
- Yale University