KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

Bloch, Michael J.; Ousingsawat, Jiraporn; Simon, Ronald; Schraml, Peter; Gasser, Thomas C.; Mihatsch, Michael J.; Kunzelmann, Karl; Bubendorf, Lukas

doi:10.1038/sj.onc.1210036

Cited by 120 publications

(114 citation statements)

References 44 publications

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“…This study also brought substantial evidences in the elucidation of the mechanisms by which IK Ca1 modulates PCa cell growth. The expression of another calcium-activated potassium channel (BK channel) in PCa cells was recently described by Bloch et al (2007). In this study, the BK potassium channel was involved in the basal cell proliferation of PC-3 cells but not of LNCaP cells, suggesting that in the LNCaP cells, only IK Ca1 calcium-activated potassium channel is involved, whereas in PC-3 cells, both IK Ca1 and BK channels participate in the modulation of the cell growth.…”

Section: Discussionmentioning

confidence: 61%

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

et al. 2009

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Accumulating data point to K þ channels as relevant players in controlling cell cycle progression and proliferation of human cancer cells, including prostate cancer (PCa) cells. However, the mechanism(s) by which K þ channels control PCa cell proliferation remain illusive. In this study, using the techniques of molecular biology, biochemistry, electrophysiology and calcium imaging, we studied the expression and functionality of intermediate-conductance calcium-activated potassium channels (IK Ca1 ) in human PCa as well as their involvement in cell proliferation. We showed that IK Ca1 mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IK Ca1 potassium channel suppressed PCa cell proliferation. The activation of IK Ca1 hyperpolarizes membrane potential and, by promoting the driving force for calcium, induces calcium entry through TRPV6, a cation channel of the TRP (Transient Receptor Potential) family. Thus, the overexpression of the IK Ca1 channel is likely to promote carcinogenesis in human prostate tissue.

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Section: Discussionmentioning

confidence: 61%

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

et al. 2009

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“…4,32,33 Our in vitro experiments using either paxilline or hSlo knockdown indicate that BK channels do not play an essential role in Cal72 cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis

Cambien

Rezzonico

Vitale

et al. 2008

Intl Journal of Cancer

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Potassium channels, the most diverse superfamily of ion channels, have recently emerged as regulators of carcinogenesis, thus introducing possible new therapeutic strategies in the fight against cancer. In particular, the large conductance Ca 21 -activated K 1 channels, often referred to as BK channels, are at the crossroads of several tumor-associated processes such as cell proliferation, survival, secretion and migration. Despite the high BK channel expression in osteosarcoma (OS), their function has not yet been investigated in this malignant bone pathology. Here, using stable RNA interference to reduce the expression of hSlo, the human pore-forming a-subunit of the BK channel, in human Cal72 OS cells, we show that BK channels play a functional role in carcinogenesis. Our results reveal for the first time that BK channels exhibit antitumoral properties in OS in vivo and affect the tumor microenvironment through the modulation of both chemokine expression and leukocyte infiltration. ' 2008 Wiley-Liss, Inc.Key words: osteosarcoma; ion channels; xenografts; chemokines; tumor microenvironmentThe development of cancer is a multistep process that usually occurs over many decades. This process encompasses the alteration of genes and/or proteins involved in fundamental cellular mechanisms like proliferation, apoptosis and differentiation. There is mounting evidence pointing to the involvement of ion channels in cancer progression. 1 The most compelling evidence regarding the involvement of ion channels in the transformation process relates to the over-expression of voltage-gated K channels in a variety of cancers. Among them are the large conductance Ca 21 -activated K 1 channels, often referred to as BK channels (for Big K). Indeed, we and others have shown that BK channels are a unique class of ion channels that are activated by a change in intracellular calcium, in voltage 2 and by a wide variety of molecules and molecular mechanisms including growth factors and hypoxia that, interestingly, are involved in carcinogenesis. [3][4][5][6] BK channels are expressed in a broad spectrum of cells in which they play a crucial role in neurotransmitter release, muscle relaxation 7,8 and diverse activities involved in tumor-associated processes such as cell proliferation, survival, secretion and migration. [9][10][11] Importantly, in human glioma, BK channels are significantly up-regulated, and their expression levels seem to correlate positively with tumor grade and poor patient prognosis. In vitro studies have suggested a role for BK channels in the control of glioma cell growth, survival and migration. 4,11 In addition glioma, we have shown a high level of BK expression in osteosarcoma (OS). 12 Altogether, these studies suggest an important role for BK in carcinogenesis and point to its potential value as a prognostic marker and/or a therapeutic target. To date, however, none of these aspects have been addressed in vivo.OS is the most common malignant bone tumor in children and adolescents. 13 OS is characterized by a hig...

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“…3B, 4), our study demonstrated that quercetin-evoked hyperpolarization is due to K ＋ efflux through BKCa activation and may eventually trigger apoptosis or inhibition of tumor cell proliferation, at least in bladder cancer cells. The involvement of BKCa in cell growth however is still controversial [26,27], although there is a close link between BKCa channels and cell proliferation [31,32] and several published data have shown involvement of BKCa channels in tumor growth in various malignant cell lines [33][34][35][36]. Abdullaev and colleagues [26] suggested that the BKCa channel lacked participation in cell proliferation in glioma cells.…”

Section: Discussionmentioning

confidence: 99%

Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca²⁺-activated K⁺Channels

Kim

Jong

2011

Korean J Physiol Pharmacol

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KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

Cited by 120 publications

References 44 publications

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis

Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca²⁺-activated K⁺Channels

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KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

Cited by 120 publications

References 44 publications

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis

Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca2+-activated K+Channels

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Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca²⁺-activated K⁺Channels