Antisense-mediated Inhibition of the plasma membrane calcium-ATPase suppresses proliferation of MCF-7 cells.
Alterations in Ca2+ signaling may contribute to tumorigenesis and the mechanism of action of some anti-cancer drugs. The plasma membrane calcium-ATPase (PMCA) is a crucial controller of intracellular Ca2+ signaling. Altered PMCA expression occurs in the mammary gland during lactation and in breast cancer cell lines. Despite this, the consequences of PMCA inhibition in breast cancer cell lines have not been investigated. In this work, we used Tet-off PMCA antisense-expressing MCF-7 cells to assess the effects of PMCA inhibition in a human breast cancer cell line. At a level of PMCA inhibition that did not completely prevent PMCA-mediated Ca2+ efflux and did not induce cell death, a dramatic inhibition of cellular proliferation was observed. Fluorescence-activated cell sorting analysis indicated that PMCA antisense involves changes in cell cycle kinetics but not cell cycle arrest. We concluded that modulation of PMCA has important effects in regulating the proliferation of human breast cancer MCF-7 cells.
Lee
Won Jae
WJ
School of Pharmacy, University of Queensland, Brisbane, Queensland 4072, Australia.
Robinson
Jodie A
JA
Holman
Nicola A
NA
McCall
Martin N
MN
Roberts-Thomson
Sarah J
SJ
Monteith
Gregory R
GR
D001943:Breast Neoplasms / Q000473:pathology*; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000502:physiology*; D027682:Cation Transport Proteins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016373:DNA, Antisense / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D027682:Cation Transport Proteins; D016373:DNA, Antisense; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases