Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells

Lee, Won Jae; Robinson, J. A.; Holman, N. A.; McCall, Martin N.; Roberts‐Thomson, Sarah J.; Monteith, Gregory R.

doi:10.1074/jbc.m414142200

Cited by 40 publications

(28 citation statements)

References 43 publications

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“…On the other hand, while the expression of PMCA4b was relatively low in control cells, it was highly upregulated upon treatments. In contrast to previous findings [53], we could not detect PMCA2 (neither PMCA3) protein expression either in control or treated MCF-7 cells using isoform specific antibodies (NR2 and NR3).…”

Section: Combined Treatment By Valerate and Pma Further Increased Pmccontrasting

confidence: 99%

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

et al. 2014

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The expression of the plasma membrane Ca 2+ ATPase (PMCA) isoforms is altered in several types of cancer cells suggesting that they are involved in cancer progression. In this study we induced differentiation of MCF-7 breast cancer cells by histone deacetylase inhibitors (HDACis) such as short chain fatty acids (SCFAs) or suberoylanilide hydroxamic acid (SAHA), and by phorbol 12-myristate 13-acetate (PMA) and found strong upregulation of PMCA4b protein expression in response to these treatments. Furthermore, combination of HDACis with PMA augmented cell differentiation and further enhanced PMCA4b expression both at mRNA and protein levels. Immunocytochemical analysis revealed that the upregulated protein was located mostly in the plasma membrane. To examine the functional consequences of elevated PMCA4b expression, the characteristics of intracellular Ca 2+ signals were investigated before and after differentiation inducing treatments, and also in cells overexpressing PMCA4b. The increased PMCA4b expression -either by treatment or overexpression -led to enhanced Ca 2+ clearance from the stimulated cells. We found pronounced PMCA4 protein expression in normal breast tissue samples highlighting the importance of this pump for the maintenance of mammary epithelial Ca 2+ homeostasis. These results suggest that modulation of Ca 2+ signaling by enhanced PMCA4b expression may contribute to normal development of breast epithelium and may be lost in cancer.3

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Section: Combined Treatment By Valerate and Pma Further Increased Pmccontrasting

confidence: 99%

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

et al. 2014

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“…Rather, a cross-talk exists between Ca 2+ signaling and various cellular signaling systems that control cell survival, proliferation, differentiation and apoptosis. An additional argument in support of this idea is the involvement of various PMCA isoforms both in cell proliferation [64,96,97] and apoptosis [9,76,98,99]. Suppressed proliferation of breast cancer MCF-7 cells or induced apoptosis in vascular smooth muscle cells via antisense-mediated PMCA inhibition were published earlier [97,99].…”

Section: Discussionmentioning

confidence: 95%

Isoform-specific up-regulation of plasma membrane Ca2+ATPase expression during colon and gastric cancer cell differentiation

Ribiczey¹,

Tordai²,

Andrikovics³

et al. 2007

Cell Calcium

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SummaryIn this work we demonstrate a differentiation-induced up-regulation of the expression of plasma membrane Ca 2+ ATPase (PMCA) isoforms being present in various gastric/colon cancer cell types. We found PMCA1b as the major isoform in non-differentiated cancer cell lines, whereas the expression level of PMCA4b was significantly lower. Cell differentiation initiated with short chain fatty acids (SCFAs) and trichostatin A, or spontaneous differentiation of post-confluent cell cultures resulted in a marked induction of PMCA4b expression, while only moderately increased PMCA1b levels. Up-regulation of PMCA4b expression was demonstrated both at the protein and mRNA levels, and closely correlated with the induction of established differentiation markers. In contrast, the expression level of the Na + /K + -ATPase or that of the sarco/endoplasmic reticulum Ca 2+ ATPase 2 protein did not change significantly under these conditions. In membrane vesicles obtained from SCFA-treated gastric/colon cancer cells a marked increase in the PMCA-dependent Ca 2+ transport activity was observed, indicating a general increase of PMCA function during the differentiation of these cancer cells.Because various PMCA isoforms display distinct functional characteristics, we suggest that upregulated PMCA expression, together with a major switch in PMCA isoform pattern may significantly contribute to the differentiation of gastric/colon cancer cells. The analysis of PMCA expression may provide a new diagnostic tool for monitoring the tumor phenotype.

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“…Monteith and his group (12) observed that the expression of different isoforms of the PMCA is changed in breast cancer cells and that PMCA2 expression is significantly increased (32). Furthermore, inhibition of PMCA using siRNA decreased proliferation of MCF-7 human breast cancer cells (33). In recent years, there has been accumulating evidence that the TRPV6 epithelial calcium entry channel is involved in breast cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen Inhibits TRPV6 Activity via Estrogen Receptor–Independent Pathways in TRPV6-Expressing MCF-7 Breast Cancer Cells

Bolanz

Kovács

Landowski

et al. 2009

Molecular Cancer Research

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The epithelial calcium channel TRPV6 is upregulated in breast carcinoma compared with normal mammary gland tissue. The selective estrogen receptor modulator tamoxifen is widely used in breast cancer therapy. Previously, we showed that tamoxifen inhibits calcium uptake in TRPV6-transfected Xenopus oocytes. In this study, we examined the effect of tamoxifen on TRPV6 function and intracellular calcium homeostasis in MCF-7 breast cancer cells transiently transfected with EYFP-C1-TRPV6. TRPV6 activity was measured with fluorescence microscopy using Fura-2. The basal calcium level was higher in transfected cells compared with nontransfected cells in calcium-containing solution but not in nominally calcium-free buffer. Basal influxes of calcium and barium were also increased. In transfected cells, 10 μmol/L tamoxifen reduced the basal intracellular calcium concentration to the basal calcium level of nontransfected cells. Tamoxifen decreased the transport rates of calcium and barium in transfected cells by 50%. This inhibitory effect was not blocked by the estrogen receptor antagonist, ICI 182,720. Similarly, a tamoxifen-induced inhibitory effect was also observed in MDA-MB-231 estrogen receptor-negative cells. The effect of tamoxifen was completely blocked by activation of protein kinase C. Inhibiting protein kinase C with calphostin C decreased TRPV6 activity but did not alter the effect of tamoxifen. These findings illustrate how tamoxifen might be effective in estrogen receptor-negative breast carcinomas and suggest that the therapeutic effect of tamoxifen and protein kinase C inhibitors used in breast cancer therapy might involve TRPV6-mediated calcium entry. This study highlights a possible role of TRPV6 as therapeutic target in breast cancer therapy.

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Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells

Cited by 40 publications

References 43 publications

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

Isoform-specific up-regulation of plasma membrane Ca2+ATPase expression during colon and gastric cancer cell differentiation

Tamoxifen Inhibits TRPV6 Activity via Estrogen Receptor–Independent Pathways in TRPV6-Expressing MCF-7 Breast Cancer Cells

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