title: Promotion of breast cancer cells MDA-MB-231 invasion by di(2-ethylhexyl)phthalate through matrix metalloproteinase-2/-9 overexpression.
abstract: Di(2-ethylhexyl)phthalate (DEHP) is an estrogenic chemical that is widely used in polyvinyl products. We aimed to determine the mechanisms behind the effects of DEHP on ERα-negative breast cancer cells MDA-MB-231 invasion and matrix metalloproteinases-2/-9 (MMP-2/-9) up-regulation in this study. Transwell assay indicated that DEHP exposure (>50 μg/ml) significantly enhanced the invasion ability of MDA-MB-231 cells. Quantitative real-time PCR (qPCR) and western blotting revealed that MMP-2/-9 is overexpressed in mRNA and protein levels after DEHP treatment. Gelatin zymography consistently demonstrated that DEHP exposure also enhances the activity of MMP-2/-9. Immunofluorescence assay showed that DEHP could accelerate NF-kappaB (NF-κB) subunits-p65 translocation into the nucleus, which is confirmed by western blotting assay, suggesting that the ratio of nuclear/cytosolic level of p65 was significantly increased. Furthermore, the invasion and MMP-2/-9 overexpression of MDA-MB-231 cells after DEHP-treated were reversed by the NF-κB chemical inhibitor JSH-23 via drug inhibition assay. This study suggested that DEHP could promote ERα-negative breast cancer cells MDA-MB-231 invasion through activating NF-κB and MMP-2/-9 overexpression.
authors: Nanjing Maternal and Child Health Institute, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.|Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China.
authors: Shuya
authors: S
authors: Zhang
authors: Department of Reproductive Health, Nanjing Maternity and Child Health Care Hospital Affiliated of Nanjing Medical University, Nanjing, 210004, China.
authors: Jiehua
authors: J
authors: Ma
authors: Nanjing Maternal and Child Health Institute, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors: Ziyi
authors: Z
authors: Fu
authors: Nanjing Maternal and Child Health Institute, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.|Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China.
authors: Zhilei
authors: Z
authors: Zhang
authors: Department of Gynecologic Endocrinology, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors: Jian
authors: J
authors: Cao
authors: The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors: Lei
authors: L
authors: Huang
authors: The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors: Wenqu
authors: W
authors: Li
authors: Nanjing Maternal and Child Health Institute, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China. pengfeixu@njmu.edu.cn.
authors: Pengfei
authors: P
authors: Xu
authors: Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China. caoxin@njmu.edu.cn.
authors: Xin
authors: X
authors: Cao
mesh_terms: D001943:Breast Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: C506487:ESR1 protein, human; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D016328:NF-kappa B; D004051:Diethylhexyl Phthalate; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Breast cancer; Di(2-ethylhexyl)phthalate; Invasion; Matrix metalloproteinases-2/-9