17‐β‐Estradiol activates maxi‐K channels through a non‐genomic pathway in human breast cancer cells

Coiret, Guyllaume; Matifat, Fabrice; Hague, Frédéric; Ouadid-Ahidouch, Halima

doi:10.1016/j.febslet.2005.02.085

Cited by 33 publications

(26 citation statements)

References 27 publications

(42 reference statements)

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“…This could explain the high sensitivity of BK channels to tamoxifen, as has already been reported for E 2 in a previous work (Coiret et al, 2005). In the same way, King et al (2006) reported that the nature of ␤ subunits that are coexpressed with ␣ subunit in human embryonic kidney 293 cells was able to influence the sensitivity of the BK channel to different kinds of steroids.…”

Section: Tamoxifen Bk Channels and Mcf-7 Cells 847supporting

confidence: 64%

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The Antiestrogen Tamoxifen Activates BK Channels and Stimulates Proliferation of MCF-7 Breast Cancer Cells

Coiret

Borowiec²,

Mariot³

et al. 2006

Mol Pharmacol

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In the present study, we investigated the effect of the antiestrogen compound tamoxifen on BK channels by the use of the patch-clamp technique. The perfusion of 10 nM tamoxifen significantly increased the magnitude of a voltage-dependent K ϩ current by 22.6 Ϯ 10.6% (n ϭ 23). The effect of tamoxifen was always obtained in the first minute, peaked at 5.9 Ϯ 2.2 min (n ϭ 23), and was abolished by the perfusion of tetraethylammonium (0.5 mM), charybdotoxin (50 nM), or iberiotoxin (100 nM). The stimulatory effect of 10 nM tamoxifen was the same at low (50 nM) and high (700 nM) internal calcium concentration and was not additive to that of 17-␤-estradiol (E 2 ) or its membrane-impermeant form, ␤-estradiol 6-(O-carboxymethyl)-oxime:bovine serum albumin. Furthermore, the effect of tamoxifen was still recorded in the presence of the selective estrogen receptor antagonist faslodex (ICI-182,780; 1 M). At the singlechannel level, tamoxifen significantly increased the open probability of the BK channel by 46.2 Ϯ 10.1% (n ϭ 4) without changing its unitary conductance. Moreover, we show here that the stimulation of BK channel activity by tamoxifen is involved in MCF-7 cell proliferation. Taken together, these results permitted us to identify the BK channel as the molecular target of tamoxifen that probably acts at the same extracellular molecular level as E 2 . The site of action of tamoxifen is probably the channel itself or the auxiliary ␤ subunits.Breast cancer is generally believed to arise when dividing cells undergo mutations, and these genetically damaged cells become susceptible to unrestrained division. Thus, female hormones and other hormones that affect growth of the mammary gland are potential risk factors for breast cancer. In contrast, factors that induce differentiation in the mammary gland, such as pregnancy and lactation, are likely to reduce the risk of breast cancer. In the case of breast cancer, estrogens are still one of the most important risk factors. Indeed, whereas 17-␤-estradiol (E 2 ) is a key growth regulator in the normal mammary gland, clinical and experimental data have clearly established that exposure to this steroid hormone is also the leading cause of sporadic female breast cancer. Thus, the usefulness of antiestrogens and/or chemopreventives is closely associated with antagonizing the activity of E 2 . The fact that estrogens may affect carcinogenesis by acting either as initiators (i.e., directly damage DNA; Liehr and Ricci, 1996) or as promoters (i.e., promoting the growth and/or survival of initiated cells; ESHRE Capri Workshop, 2004;Veronesi et al., 2005) has justified the use of antiestrogenic compounds such as tamoxifen in estrogenic hormone replacement therapy. However, in addition to their key role in female reproductive functions, estrogens have beneficial effects on unrelated tissues, as demonstrated by the effects of hormone replacement therapy on postmenopausal women (Mitlack and Cohen, 1997;Cosman and Lindsay, 1999). Indeed, estrogens can prevent osteoporosis by inhibitin...

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Section: Tamoxifen Bk Channels and Mcf-7 Cells 847supporting

confidence: 64%

“…Many types of K ϩ channels have been shown to be involved in the progression of the cell cycle and proliferation of MCF-7 cell line (Ouadid-Ahidouch et al, 2000, 2004aCoiret et al, 2005). We show here that tamoxifen stimulates MCF-7 cell proliferation through a direct modulation of BK channels independently of its ER antagonist properties.…”

Section: Discussionmentioning

confidence: 63%

The Antiestrogen Tamoxifen Activates BK Channels and Stimulates Proliferation of MCF-7 Breast Cancer Cells

Coiret

Borowiec²,

Mariot³

et al. 2006

Mol Pharmacol

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“…Pardo, 2004;Afrasiabi et al, 2010]. Generally and unequivocally, a diversity of K þ channel subunits has been identified to be of fundamental and vital importance for breast cancer cells [Coiret et al, 2005[Coiret et al, , 2007Hemmerlein et al, 2006;vanTol et al, 2007;Ouadid-Ahidouch and Ahidouch, 2008;Roy et al, 2008]. Future studies will show the functional role(s) of GIRK proteins produced by the alternative splicing of the KCNJ3 gene in the pathophysiology of breast cancer cells.…”

Section: Discussionmentioning

confidence: 95%

Cloning and characterisation of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line

Wagner

Stadelmeyer

Riederer

et al. 2010

J of Cellular Biochemistry

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The aim of this study was to investigate the impact of increased mRNA levels encoding GIRK1 in breast tumours on GIRK protein expression. mRNA levels encoding hGIRK1 and hGIRK4 in the MCF7, MCF10A and MDA-MB-453 breast cancer cell lines were assessed and the corresponding proteins detected using Western blots. cDNAs encoding for four hGIRK1 splice variants (hGIRK1a, 1c, 1d and 1e) were cloned from the MCF7 cell line. Subcellular localisation of fluorescence labelled hGIRK1a-e and hGIRK4 and of endogenous GIRK1 and GIRK4 subunits was monitored in the MCF7 cell line. All hGIRK1 splice variants and hGIRK4 were predominantly located within the endoplasmic reticulum. Heterologous expression in Xenopus laevis oocytes and two electrode voltage clamp experiments together with confocal microscopy were performed. Only the hGIRK1a subunit was able to form functional GIRK channels in connection with hGIRK4. The other splice variants are expressed, but exert a dominant negative effect on heterooligomeric channel function. Hence, alternative splicing of the KCNJ3 gene transcript in the MCF7 cell line leads to a family of mRNA's, encoding truncated versions of the hGIRK1 protein. The very high abundance of mRNA's encoding GIRK1 together with the presence of GIRK1 protein suggests a pathophysiological role in breast cancer.

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“…Missing activation of BK and lack of stimulation of cell proliferation by 17b-estradiol in PC-3 cells suggests that BK channels operate at maximal activity in these cells owing to overexpression driven by amplification. Interestingly, it has recently been shown that a proliferative effect of 17b-estradiol in the breast cancer cell line MCF-7 is also mediated by BK channels independently of estrogen receptor (Coiret et al, 2005). PC-3 and BPH-1 are known to express estrogen receptor alpha and beta, whereas LNCaP only expresses the estrogen receptor beta (Lau et al, 2000).…”

Section: Kcnma1 Amplification In Prostate Cancermentioning

confidence: 99%

KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

et al. 2006

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17‐β‐Estradiol activates maxi‐K channels through a non‐genomic pathway in human breast cancer cells

Cited by 33 publications

References 27 publications

The Antiestrogen Tamoxifen Activates BK Channels and Stimulates Proliferation of MCF-7 Breast Cancer Cells

The Antiestrogen Tamoxifen Activates BK Channels and Stimulates Proliferation of MCF-7 Breast Cancer Cells

Cloning and characterisation of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line

KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

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