Estrogen receptor alpha as a key target of organochlorines to promote angiogenesis

Autor: Yves Malthièry, Sébastien Faure, Ramaroson Andriantsitohaina, Emilie Lauret, Nicolas Clere
Přispěvatelé: Univ Angers, Okina, Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)
Rok vydání: 2012
Předmět:
Male
Cancer Research
Physiology
Angiogenesis
[SDV]Life Sciences [q-bio]
Clinical Biochemistry
Pro-angiogenic
Estrogen receptor
medicine.disease_cause
Neovascularization
Mice
0302 clinical medicine
Hydrocarbons
Chlorinated
Cells
Cultured
Cancer
0303 health sciences
Microscopy
Confocal
Flow Cytometry
3. Good health
[SDV] Life Sciences [q-bio]
Endothelial stem cell
Oncology
Chlordecone
030220 oncology & carcinogenesis
RNA Interference
medicine.symptom
medicine.medical_specialty
Cardiology
Neovascularization
Physiologic
Biology
Endothelial
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
Pesticides
Cell adhesion
030304 developmental biology
Electron Spin Resonance Spectroscopy
Estrogen Receptor alpha
Lindane
Estrogen
Biomedicine
Ophthalmology
Endocrinology
Cancer research
Tumor promotion
Cell
Carcinogenesis
Estrogen receptor alpha
Zdroj: Angiogenesis
Angiogenesis, Springer Verlag, 2012, 15 (4), pp.745-760. ⟨10.1007/s10456-012-9288-7⟩
ISSN: 1573-7209
0969-6970
Popis: International audience; Epidemiological studies report that exposure to pesticides like chlordecone and lindane increases risk of cancer. They may act as endocrine disruptors via the activation of estrogen receptor α (ERα). Carcinogenesis involved angiogenesis and no available data regarding these organochlorines have been reported. The present study aimed at investigating the effects of lindane and chlordecone on cellular processes leading to angiogenesis through an involvement of ERα. Angiogenesis has been analyzed both in vitro, on human endothelial cells, and in vivo by quantifying neovascularization with the use of ECMgel® plug in mice. Both pesticides increased endothelial cell proliferation, migration and MMP2 activity. These toxics potentiated cell adhesion by enhancing FAK phosphorylation and stress fibers. The two organochlorines increased nitric oxide production via an enhancement of eNOS activity without modification of oxidative stress. Evidence has been provided that the two toxins increased in vivo neovascularization. Most interestingly, all the above processes were either partially or completely prevented after silencing of ERα. Altogether, these data highlight that organochlorines modulate cellular angiogenic processes through activation of ERα. This study further reinforces the harmful effects of these pesticides in carcinogenesis, particularly in the modulation of angiogenesis, a critical step in tumor promotion, through ERα.
Databáze: OpenAIRE
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