کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2600591 1133275 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An endocrine-disrupting chemical, fenvalerate, induces cell cycle progression and collagen type I expression in human uterine leiomyoma and myometrial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
An endocrine-disrupting chemical, fenvalerate, induces cell cycle progression and collagen type I expression in human uterine leiomyoma and myometrial cells
چکیده انگلیسی

Fenvalerate (Fen), widely used for its high insecticidal potency and low mammalian toxicity, is classified as an endocrine-disrupting chemical. Recently, Fen has received great attention for its adverse effects on human reproductive health. In this study, we found that Fen (10 μM) had a stimulatory effect on the growth of both cell lines at 24 h compared with controls by MTS (p < 0.01) and BrdU (p < 0.01) assays in hormonally responsive uterine leiomyoma (UtLM) cells and normal uterine smooth muscle cells (UtSMC). Flow cytometry results showed that Fen enhanced the escape of cells from the G0–G1 checkpoint and promoted progression of both cell types into the S phase. An Annexin V assay showed that Fen had an anti-apoptotic effect on both cell types. By Real-time PCR, we found that collagen I mRNA expression increased (p < 0.05) in Fen-treated cells compared to controls, although it was greater in UtLM tumor cells. Accordingly, Fen increased (p < 0.05) collagen I protein levels in both cell lysate and supernatant when compared to controls. To further test the mechanism of Fen's effects, transactivation and competitive binding assays were done. The results showed Fen did not significantly stimulate luciferase activity at concentrations of 0.1 μM, 1.0 μM or 10.0 μM in either of the cell types. Competitive binding assays revealed that the affinity of Fen binding to estrogen receptors (ERs) was non-detectable compared to E2. Our data show that Fen can stimulate the growth of both UtLM cells and UtSMC, which involves a combination of enhanced cell cycle progression and inhibition of apoptosis. Also this compound can increase collagen I expression, at both mRNA and protein levels. Interestingly, the ER is less likely involved in either the hyperplasia or extracellular matrix (ECM) overproduction induced by Fen. Our results indicate that Fen exposure could be considered a novel risk factor for uterine fibroids through molecular mechanisms that do not directly involve the ERs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 196, Issue 3, 15 July 2010, Pages 133–141
نویسندگان
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