Estrogens decrease γ-ray–induced senescence and maintain cell cycle progression in breast cancer cells independently of p53

Toillon, Robert‐Alain; Magné, Nicolas; Laı̈os, Ioanna; Castadot, Pierre; Kinnaert, Eric; Houtte, Paul Van; Desmedt, Christine; Leclercq, Guy; Lacroix, Marc

doi:10.1016/j.ijrobp.2006.11.040

Cited by 18 publications

(13 citation statements)

References 47 publications

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“…This is consistent with observations of ERα activity leading to the accumulation of DNA damage (1) as it would sustain proliferation by not engaging the ATM/ATR pathways, while promoting DNA-PK-mediated NHEJ to maintain genome integrity. Toillon et al found that estrogen treatment of irradiated breast cancer cells led to their sustained proliferation without any increase in p53 activation or apoptosis (20). This is consistent with a failure to activate ATM or ATR but the repair of DNA by DNA-PK mediated NHEJ.…”

Section: Dna Damage Response and Dna Repair Pathways Altered By Estromentioning

confidence: 99%

“…When estrogen treated breast cancer cells are irradiated there is partial activation of p53 and its downstream pathways, but the pro-proliferative effects of estrogen override any checkpoint-mediated cell cycle arrest (20). Conversely, in mouse models, p53 provides protection from lymph node hyperplasia and ductal carcinoma in situ (DCIS) induced by deregulated estrogen signaling (48).…”

Section: Dna Damage Response and Dna Repair Pathways Altered By Estromentioning

confidence: 99%

“…The outcome will be dictated by the strength of each signal, but ERα signaling is able to sustain proliferation in situations where otherwise DNA damage would have induced a cell cycle arrest and apoptosis (15, 20, 66). …”

Section: Dna Damage Response and Dna Repair Pathways Altered By Estromentioning

confidence: 99%

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Estrogen Signaling and the DNA Damage Response in Hormone Dependent Breast Cancers

2014

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Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR) and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1, and p53 and the feedback on estrogen receptor signaling from these proteins. We put forward the hypothesis that estrogen receptor signaling converges to suppress effective DNA repair and apoptosis in favor of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer, which will further change the processing of DNA damage. Finally, the action of estrogen signaling on DNA damage is also relevant to the therapeutic setting as the suppression of a DDR by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.

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Section: Dna Damage Response and Dna Repair Pathways Altered By Estromentioning

confidence: 99%

Section: Dna Damage Response and Dna Repair Pathways Altered By Estromentioning

confidence: 99%

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Estrogen Signaling and the DNA Damage Response in Hormone Dependent Breast Cancers

2014

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“…Clonogenic assays were performed as previously described [21]. Briefly, MCF-7 and MDA-MB-231 cells were plated at a density of 25,000/dish in 35 mm dishes and cultured in basal DMEM medium without phenol red and supplemented with 10% inactivated and charcoal-dextran stripped FCS.…”

Section: Clonogenic Assaysmentioning

confidence: 99%

A ferrocenyl derivative of hydroxytamoxifen elicits an estrogen receptor-independent mechanism of action in breast cancer cell lines

Vessières

Corbet

Heldt

et al. 2010

Journal of Inorganic Biochemistry

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“…Inhibition of Akt signalling causes protection of cells against photocarcinogenesis via modulation of the cell cycle [24]. On the other hand, estradiol down-regulates p21 waf1 synthesis and dephosphorylates Rb to decrease g-ray-induced cell cycle arrest independent of p53 [25]. PTEN is a member of the protein tyrosine phosphatase family and reverses the action of phospoinositide 3-kinase [26] and its depletion prevents the tumour suppression through activation of the PI3K/Akt pathway [27].…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone augments sensitivity toγ-ray irradiation in human H4 neuroglioma cells through down-regulation of Akt signaling

Hirao¹,

Urata²,

Kageyama³

et al. 2008

Free Radical Research

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Dehydroepiandrosterone (DHEA) modulates sensitivity to radiation-induced injury in human neuroglioma cells (H4) through effects on Akt signalling by glutathione (GSH)-dependent redox regulation. Previous treatment of H4 cells with DHEA for 18 h reduced the gamma-ray-induced phosphorylation of Akt, activated p21(waf1) synthesis and up-regulated phosphorylation of Rb independent of p53. These reactions were followed by a decrease in cell number and an increase in apoptosis and G(2)/M checkpoint arrest. The suppression of phosphorylation of Akt by DHEA was due to regulation of the dephosphorylation by protein phosphatase 2A (PP2A). DHEA up-regulated the expression of gamma-glutamylcysteine synthetase, a rate-limiting enzyme of glutathione (GSH) synthesis, and the levels of GSH to maintain PP2A activity. The results suggested that DHEA increases the sensitivity of cells to gamma-ray irradiation by inducing apoptosis and cell cycle arrest through GSH-dependent regulation of the reduced form of PP2A to down-regulate the Akt signalling pathway.

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Estrogens decrease γ-ray–induced senescence and maintain cell cycle progression in breast cancer cells independently of p53

Cited by 18 publications

References 47 publications

Estrogen Signaling and the DNA Damage Response in Hormone Dependent Breast Cancers

Estrogen Signaling and the DNA Damage Response in Hormone Dependent Breast Cancers

A ferrocenyl derivative of hydroxytamoxifen elicits an estrogen receptor-independent mechanism of action in breast cancer cell lines

Dehydroepiandrosterone augments sensitivity toγ-ray irradiation in human H4 neuroglioma cells through down-regulation of Akt signaling

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