Document Detail

Mono-(2-ethylhexyl) phthalate (MEHP) promotes invasion and migration of human testicular embryonal carcinoma cells.
MedLine Citation:
PMID:  22321834     Owner:  NLM     Status:  MEDLINE    
Testicular dysgenesis syndrome refers to a collection of diseases in men, including testicular cancer, that arise as a result of abnormal testicular development. Phthalates are a class of chemicals used widely in the production of plastic products and other consumer goods. Unfortunately, phthalate exposure has been linked to reproductive dysfunction and has been shown to adversely affect normal germ cell development. In this study, we show that mono-(2-ethylhexyl) phthalate (MEHP) induces matrix metalloproteinase 2 (MMP2) expression in testicular embryonal carcinoma NT2/D1 cells but has no significant effect on MMP9 expression. NT2/D1 cells also have higher levels of MYC expression following MEHP treatment. It is widely recognized that activation of MMP2 and MYC is tightly associated with tumor metastasis and tumor progression. Gelatin zymographic analysis indicates that MEHP strongly activates MMP2 in NT2/D1 cells. Addition of the MMP2-specific inhibitor SB-3CT inhibited MEHP-enhanced cell invasion and migration, demonstrating that MMP2 plays a functional role in promoting testicular embryonal carcinoma progression in response to MEHP exposure. Furthermore, we investigated genome-wide gene expression profiles of NT2/D1 cells following MEHP exposure at 0, 3, and 24 h. Microarray analysis and semiquantitative RT-PCR revealed that MEHP exposure primarily influenced genes in cell adhesion and transcription in NT2/D1 cells. Gap junction protein-alpha 1, vinculin, and inhibitor of DNA-binding protein-1 were significantly down-regulated by MEHP treatment, while claudin-6 and beta 1-catenin expression levels were up-regulated. This study provides insight into mechanisms that may account for modulating testicular cancer progression following phthalate exposure.
Pei-Li Yao; Yi-Chen Lin; John H Richburg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-31
Journal Detail:
Title:  Biology of reproduction     Volume:  86     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-09-17     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  160, 1-10     Citation Subset:  IM    
Center for Molecular and Cellular Toxicology, Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
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MeSH Terms
Catenins / biosynthesis
Cell Adhesion / drug effects,  physiology
Cell Line, Tumor
Cell Movement / drug effects,  physiology*
Claudins / biosynthesis
Connexin 43 / biosynthesis
Diethylhexyl Phthalate / adverse effects,  analogs & derivatives*
Embryonal Carcinoma Stem Cells / drug effects,  pathology*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects,  physiology
Heterocyclic Compounds, 1-Ring / pharmacology
Inhibitor of Differentiation Protein 1 / biosynthesis
Matrix Metalloproteinase 2 / biosynthesis
Matrix Metalloproteinase 9 / biosynthesis
Neoplasm Invasiveness
Sulfones / pharmacology
Testicular Neoplasms / drug therapy,  pathology*
Transcription, Genetic / drug effects,  physiology
Vinculin / biosynthesis
Grant Support
Reg. No./Substance:
0/Catenins; 0/Claudins; 0/Connexin 43; 0/GJA1 protein, human; 0/Heterocyclic Compounds, 1-Ring; 0/ID1 protein, human; 0/Inhibitor of Differentiation Protein 1; 0/SB 3CT compound; 0/Sulfones; 0/claudin 6; 0/delta catenin; 117-81-7/Diethylhexyl Phthalate; 125361-02-6/Vinculin; 4376-20-9/mono-(2-ethylhexyl)phthalate; EC protein, human; EC Metalloproteinase 2; EC Metalloproteinase 9

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