Xenoestrogen regulation of ERα/ERβ balance in hormone-associated cancers

Acconcia, Filippo; Fiocchetti, Marco; Marino, Maria

doi:10.1016/j.mce.2016.10.033

Cited by 46 publications

(61 citation statements)

References 150 publications

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“…Some ERα ligands (e.g., 4OH-tamoxifen and faslodex) change ERα levels and block E2induced cell proliferation. Recently, we and others have also shown that the interference with pathways not related to ERα obtained by specific molecules (e.g., chloroquine) or by selective gene knock-down (e.g., siRNA against clathrin, caveolins, and dynamin II) modifies ERα intracellular content and prevents E2 proliferative effects [1,4,[11][12][13][14][15][16][17][18]. On this basis, we have proposed [1,11,25] that the modulation of ERα intracellular concentration in BC cells could be used as a pharmacological target to identify anti-tumor drugs.…”

Section: Mcf-7 Cellsmentioning

confidence: 97%

A functional drug re-purposing screening identifies carfilzomib as a drug preventing 17β-estradiol: ERα signaling and cell proliferation in breast cancer cells

Busonero

Leone

Klemm

et al. 2017

Preprint

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Section: Mcf-7 Cellsmentioning

confidence: 97%

A functional drug re-purposing screening identifies carfilzomib as a drug preventing 17β-estradiol: ERα signaling and cell proliferation in breast cancer cells

Busonero

Leone

Klemm

et al. 2017

Preprint

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“…17β‐estradiol (E2) is a master regulator of human physiology both in males and infemales. E2 binds to the estrogen receptors (i.e., ERα and ERβ), which mediate a plethora of physiological effects including cell proliferation, with ERα promoting cell proliferation and ERβ having anti‐proliferative and differentiation roles (Acconcia, Fiocchetti, & Marino, ). The E2‐activated ERs signal through diverse multifaceted mechanisms: the nuclear‐localized ERα and ERβ control, as ligand‐activated transcription factors, gene transcription profiles in response to E2 (i.e., nuclear effects).…”

Section: Introductionmentioning

confidence: 99%

“…ERα and ERβ are also extrinsic plasma membrane proteins that engage E2 and trigger the activation of extra‐nuclear signals (e.g., PI3 K/AKT, ERK/MAPK pathways). Nuclear and extra‐nuclear mechanisms are intertwined and are both necessary for normal cell and organ functions in vivo (Acconcia et al, , ; Adlanmerini et al, ; Ascenzi, Bocedi, & Marino, ; La Rosa, Pesiri, Leclercq, Marino, & Acconcia, ; Levin & Hammes, ; Pedram, Razandi, Lewis, Hammes, & Levin, ). ERα and ERβ intracellular levels are also finely regulated by E2, which induces ERα degradation and increases ERβ intracellular concentration.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, E2 signaling and its resulting physiological effects are also a function of the temporal changes in ERs cell content. In turn, many endocrine‐related pathologies show deregulated E2 intracellular signaling and/or control of ERs intracellular concentration (Acconcia et al, ; Leclercq, Lacroix, Laios, & Laurent, ; Thomas & Gustafsson, ).…”

Section: Introductionmentioning

confidence: 99%

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A high throughput method to study the physiology of E2:ERα signaling in breast cancer cells

Leone

Busonero

Acconcia

2017

Journal Cellular Physiology

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17β-estradiol (E2) regulates diverse physiological effects including cell proliferation through the estrogen receptor α (ERα), which as a transcription factor drives gene transcription and as an extra-nuclear localized receptor triggers the membrane-dependent activation of diverse kinase cascades. E2 also modifies ERα intracellular levels via diverse intracellular mechanisms. In this way, the E2-acivated ERα integrates signaling cascades with the modulation of receptor intracellular concentration and with the induction of DNA synthesis and ultimately drives cell proliferation. In turn, E2 signaling deregulation can cause many diseases including breast cancer (BC). Recently, we performed a Western blotting (WB)-based screen to identify novel pathways affecting ERα intracellular levels and BC cell proliferation. However, because WB lacks high throughput potential, a high-content method to detect all aspects of E2:ERα signaling (nuclear and extra-nuclear receptor activity, ERα levels, E2-induced DNA synthesis) is desirable. Here, we set up a rapid way to measure E2:ERα signaling in 96-well plate format. To demonstrate its robustness, we also challenged 4OH-tamoxifen resistant (Tam-Res) BC cells with a library of anti-cancer drugs and identified methotrexate (MTX) as a molecule inducing ERα degradation and preventing BC cell proliferation. Overall, our research provides a high-content technique to study the physiology of E2:ERα signaling in cells and further suggests a possible anti-ERα and anti-proliferative use for MTX in Tam-Res BCs.

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“…BPA has structural similarity to the synthetic estrogen diethylstilbestrol (DES) and consequently has estrogenic activity but substantially weaker than DES and natural estrogen 27,28 . BPA is capable of mimicking like endogenous estrogens and interacting with their receptors in a variety of fashions, and because of this, adverse neuro-developmental, reproductive, cancerous, and metabolic outcomes have been reported in various studies 29,30,31 . Recently, studies reported that BPA believed to disturb bone metabolism.…”

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confidence: 99%

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2019

IJPSR

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Bisphenol-A (BPA), 2,2-bis(4-hydroxyphenyl) propane is an emerging environmental toxicant with endocrine disrupting properties and toxic effects on living organisms. BPA is ubiquitously present in consumer products current in our daily lives. As it is released from consumer products and deposited in the environment, thus creating the potential for human exposure through oral, inhaled, and dermal routes. BPA exposure might be able to cause oxidative damage by disturbing the balance between reactive oxygen species (ROS) and the antioxidant defense system of eukaryotic cells, resulting in the development of oxidative stress-related diseases. From the available information, it can be inferred that a wide variety of BPA intake through any mode results into a generation of reactive oxygen species (ROS), altering the antioxidant balance of eukaryotic cells, induces mitochondrial dysfunction, and affects cell signaling pathways related to oxidative stress. BPA induced oxidative stress might be able to cause sperm damage, mitochondrial dysfunction, and impairment of the structure and function of spermatozoa resulting in male infertility. Here, a review of the current literature examining literature related to BPA exposure, induction of ROS or oxidative stress and concludes that it alters reproductive system functions through induced oxidative stress pathways and negatively affects the fertility of male and females.

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Xenoestrogen regulation of ERα/ERβ balance in hormone-associated cancers

Cited by 46 publications

References 150 publications

A functional drug re-purposing screening identifies carfilzomib as a drug preventing 17β-estradiol: ERα signaling and cell proliferation in breast cancer cells

A functional drug re-purposing screening identifies carfilzomib as a drug preventing 17β-estradiol: ERα signaling and cell proliferation in breast cancer cells

A high throughput method to study the physiology of E2:ERα signaling in breast cancer cells

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