Estrogen induces phospholipase A2 activation through ERK1/2 to mobilize intracellular calcium in MCF-7 cells

Thomas, Warren; Coen, Natasha; Faherty, Sheila; Flatharta, Cathal Ó; Harvey, Bill

doi:10.1016/j.steroids.2005.10.010

Cited by 43 publications

(27 citation statements)

References 59 publications

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“…The sPLA2-IIa activates the MAP kinase pathway [52], which is specifically related to human BC evolution [53,54]. Interestingly, the significantly lower expression of sPLA2-IIa in post-menopausal women with BC is in agreement with recent evidence that 17b-estradiol induces PLA2 activation in hormone-dependent BC cells [45], as well as in other tissues [46], and that tamoxifen (an antiestrogen agent) down-regulates sPLA2-IIa [49]. These AA-based eicosanoid signalling pathways may be crucial to provide specific substrates for inducible COX enzymes (e.g., COX-2) catalyzing the conversion of AA to several PGs [24,25,36].…”

Section: Discussionsupporting

confidence: 87%

“…An explanation may be linked to a possible influence of hormonal status on sPLA2-IIa activity. In fact, several studies evidenced that PLA2 activity is modulated by both agonists and antagonists of steroid hormones (e.g., 17b-estradiol, progesterone, and tamoxifen), in breast as well as in other tissues [45][46][47][48]. Another possible mechanism may be related to the significant expression of Annexin II (an endogeneous inhibitor of PLA2 activity) in breast cancer tissues respect to the undetectable levels in normal and hyperplastic breast ductal epithelial cells [49]; the dysregulated balance between sPLA2-IIa activity and its inhibition by annexins has been proposed in the pathogenesis of prostate cancer [50].…”

Section: Discussionmentioning

confidence: 99%

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Nipple aspirate fluids from women with breast cancer contain increased levels of group IIa secretory phospholipase A2

Mannello

Qin

Zhu

et al. 2007

Breast Cancer Res Treat

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Arachidonic acid, a bioactive molecule metabolized into prostaglandins and leukotrienes, contributes to cellular proliferation and tumor progression. Group IIa secretory phospholipase A2 (sPLA2-IIa) can facilitate arachidonate release from cellular phospholipids, suggesting its involvement in tumor evolution. Analysis of breast nipple aspirate fluid (NAF), a noninvasive research tool, allows the identification of biomarkers of breast cancer. We sought to determine whether sPLA2-IIa expression might be related to breast cancer development or progression. sPLA2-IIa expression was evaluated in NAF samples from 110 women (57 women with and 53 without breast cancer) using ELISA and western blotting; ultrastructural immunolocalization was performed in epithelial cells floating in NAF. Immunocytochemistry revealed that sPLA2-IIa is a constitutive intracellular protein suggesting that breast ductal cells synthesize and secrete the 14 kDa protein in NAF. Among all 110 subjects, sPLA2-IIa expression was significantly increased both in NAF and within ductal epithelial cells from cancer containing breasts. While in healthy women menopausal status did not influence sPLA2-IIa expression (P = 0.457), among patients with breast cancer there was a significant down-regulation in postmenopausal subjects (P < 0.0001). Moreover, sPLA2-IIa concentration in NAF from breast cancer patients was positively correlated with tumor stage (r (2) = 0.979, P = 0.0012), suggesting an active secretion/accumulation of the enzyme in NAF based on tumor burden. sPLA2-IIa activity may serve a dual role in breast carcinogenesis, beneficial in its release of arachidonate and detrimental in the metabolic conversion of arachadonic acid into prostaglandins and leukotrienes.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Nipple aspirate fluids from women with breast cancer contain increased levels of group IIa secretory phospholipase A2

Mannello

Qin

Zhu

et al. 2007

Breast Cancer Res Treat

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“…Intracellular regulatory cascades such as extracellular signal-regulated kinase/ mitogen-activated protein kinases (ERK/MAPK) and PI3-K have been shown to be stimulated by estrogen in diverse cell types, such as tumor cells and neurons [30,39,40,43]. A non-transcriptional mechanism for ER signaling in human as well as in animal endothelial cells was also described, showing that ER can physically and functionally couple to PI3K.…”

Section: Discussionmentioning

confidence: 99%

“…Earlier mERs were implicated in mediating a rapid rise of intracellular free [Ca 2? ] i in T cells and in MCF7 tumor cell line [30,31]. Therefore, we tested the effect of bE2 and bE2-BSA on [Ca 2? ]…”

Section: Be2 Induces Oscillating Ca 2? -Signals In T Cells But Not Inmentioning

confidence: 99%

Estrogen augments the T cell-dependent but not the T-independent immune response

Ádori

Kiss

Barad

et al. 2010

Cell. Mol. Life Sci.

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Estrogen plays a critical regulatory role in the development and maintenance of immunity. Its role in the regulation of antibody synthesis in vivo is still not completely clear. Here, we have compared the effect of estrogen on T cell-dependent (TD) and T cell-independent type 2 (TI-2) antibody responses. The results provide the first evidence that estrogen enhances the TD but not the TI-2 response. Ovariectomy significantly decreased, while estrogen re-administration increased the number of hapten-specific IgM- and IgG-producing cells in response to TD antigen. In vitro experiments also show that estrogen may have a direct impact on B and T cells by inducing rapid signaling events, such as Erk and AKT phosphorylation, cell-specific Ca(2+) signal, and NFkappaB activation. These non-transcriptional effects are mediated by classical estrogen receptors and partly by an as yet unidentified plasma membrane estrogen receptor. Such receptor- mediated rapid signals may modulate the in vivo T cell-dependent immune response.

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“…The MCF-7 cells were purchased from ATCC and cultured in Eagle's Minimum Essential Medium (EMEM), with 10% fetal bovine serum, L-glutamine at 37 o , according ATCC guidelines. 70-80% confluent MCF-7 cells were placed in serum-free EMEM overnight, and then stimulated with the designated compounds for western blotting, immunoprecipitation, ELISA, or luciferase assays as indicated.…”

Section: Cell Culturementioning

confidence: 99%

Estrogen Activation of CaM Kinases and Transcription Is Blocked by Vitamin D in MCF-7 Breast Cancer Cells

John¹,

Do²,

Amanda³

et al. 2017

JAMB

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Abstract. Calcium/calmodulin-dependent protein kinase (CaM Kinase) proteins are targets of hormones and growth factors and regulate cancer cell growth, apoptosis and migration. The hormone estrogen (E2) utilizes CaM Kinases to activate the Extracellular-signal regulated kinase (ERK) leading to MCF-7 breast cancer cell growth. The hormone Vitamin D (Vit D) may inhibit breast cancer cell growth however the cellular mechanisms of Vit D action remain to be elucidated. Within the present study we provide data that E2 stimulation of MCF-7 cells activates CaM Kinase Kinase (CaM KK), CaM KI, and ERK and the transcription factors Elk-1 and SRF. E2 treatment of MCF-7 cells potently stimulated Elk-1/SRF directed transcription of SRE-luciferase reporters. E2 activation of ERK, Elk-1, SRF and SRE-dependent luciferase activities were blocked by treating cells with the CaM KK inhibitor, STO-609, and the ERK inhibitor, U0126. Moreover, siRNAs directed against CaM KK and ERK blocked transcription factor phosphorylation and luciferase activity. Treatment of cells with Vit D, the hormone Epinephrine (Epi), or Forskolin, prevented E2 activation of CaM KK and ERK. Interestingly, Vit D promoted a PKA-dependent phosphorylation and inhibition of CaM KK as well as its association with 14-3-3. Epi and Vit D treatment of cells blocked the ability of E2 to active Elk-1 and SRE-luciferase activity. This data suggests an important role for CaM KK and ERK in regulating transcription downstream of E2 in MCF-7 cells. Our results also suggest that Vit D treatment of MCF-7 cells utilizes a unique PKA-dependent mechanism to block E2 activation of CaM KK, ERK and transcription.

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Estrogen induces phospholipase A2 activation through ERK1/2 to mobilize intracellular calcium in MCF-7 cells

Cited by 43 publications

References 59 publications

Nipple aspirate fluids from women with breast cancer contain increased levels of group IIa secretory phospholipase A2

Nipple aspirate fluids from women with breast cancer contain increased levels of group IIa secretory phospholipase A2

Estrogen augments the T cell-dependent but not the T-independent immune response

Estrogen Activation of CaM Kinases and Transcription Is Blocked by Vitamin D in MCF-7 Breast Cancer Cells

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