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Originally published In Press as doi:10.1074/jbc.M414142200 on May 23, 2005

J. Biol. Chem., Vol. 280, Issue 29, 27076-27084, July 22, 2005
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Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells*

Won Jae Lee{ddagger}, Jodie A. Robinson{ddagger}, Nicola A. Holman{ddagger}, Martin N. McCall§, Sarah J. Roberts-Thomson{ddagger}, and Gregory R. Monteith{ddagger}

From the {ddagger}School of Pharmacy, University of Queensland, Brisbane, Queensland 4072, Australia and §Acyte Biotech Pty. Ltd., Sydney, New South Wales 2052, Australia

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.


Received for publication, December 16, 2004 , and in revised form, April 15, 2005.

* This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (102426), the Queensland Cancer Fund (Q34-02), and by a Dora Lush (Biomedical) Postgraduate Research Scholarship (awarded to W. J. L.) by the NHMRC.

To whom correspondence should be addressed: School of Pharmacy, University of Queensland, Steele Bldg., Brisbane, Queensland 4072, Australia. Tel.: 61-7-3365-7442; Fax: 61-7-3365-1688; E-mail: G.Monteith{at}pharmacy.uq.edu.au.


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