Plasma membrane calcium ATPase 4 and the remodeling of calcium homeostasis in human colon cancer cells

Aung, Cho S., Ye, Weilan, Plowman, Greg, Peters, Amelia A., Monteith, Gregory R. and Roberts-Thomson, Sarah J. (2009) Plasma membrane calcium ATPase 4 and the remodeling of calcium homeostasis in human colon cancer cells. Carcinogenesis, 30 11: 1962-1969. doi:10.1093/carcin/bgp223

Author Aung, Cho S.
Ye, Weilan
Plowman, Greg
Peters, Amelia A.
Monteith, Gregory R.
Roberts-Thomson, Sarah J.
Title Plasma membrane calcium ATPase 4 and the remodeling of calcium homeostasis in human colon cancer cells
Journal name Carcinogenesis   Check publisher's open access policy
ISSN 0143-3334
Publication date 2009-11-01
Year available 2009
Sub-type Article (original research)
DOI 10.1093/carcin/bgp223
Open Access Status Not Open Access
Volume 30
Issue 11
Start page 1962
End page 1969
Total pages 8
Editor A. Clarke
C. C. Harris
Place of publication United Kingdom
Publisher Oxford University Press
Language eng
Subject C1
111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
920102 Cancer and Related Disorders
Formatted abstract
A remodeling of calcium homeostasis has been identified as a characterizing feature of some cancers. Possible consequences of this include alterations in many pivotal physiological responses including apoptosis, proliferation and gene transcription. An alteration in calcium homeostasis can occur via changes in the expression of proteins that transport calcium and examples of cancers where this is seen includes the prostate and breast. A specific isoform of the calcium efflux pump, plasma membrane Ca2+-ATPase (PMCA) 4, is significantly upregulated during differentiation of the HT-29 colon cancer cell line suggesting that it may also be altered in colon cancer. We now report that differentiated HT-29 colon cancer cells have pronounced plasma membrane PMCA4 localization, consistent with augmented calcium efflux. Assessment of PMCA4 transcription in human colon cancer samples suggests that PMCA4 is significantly (P < 0.000001) downregulated early in the progression of some colon cancers as these cells become less differentiated. Inhibition of PMCA4 using small interfering RNA did not induce cell death or augment sensitivity to the mitochondrial uncoupler carbonyl cyanide 3-chlorophenylhydrazone (CCCP) or tumor necrosis factor-related apoptosis-inducing ligand. Reversing the colon cancer remodeling of PMCA4 by overexpression reduced cellular proliferation (P < 0.01) and downregulated transcription of the calcium sensitive early response gene FOS. Our studies suggest that the remodeling of the calcium signal in colon cancer is associated with compromised calcium efflux at a level that promotes proliferative pathways while avoiding increased sensitivity to apoptotic stimuli.
Keyword trail-induced apoptosis
sperm motility
early event
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 569645
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 33 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 12 Jan 2010, 00:12:02 EST by Charna Kovacevic on behalf of School of Pharmacy