An alkylphenol mix promotes seminoma derived cell proliferation through an ERalpha36-mediated mechanism

Long chain alkylphenols are man-made compounds still present in industrial and agricultural processes. Their main use is domestic and they are widespread in household products, cleansers and cosmetics, leading to a global environmental and human contamination. These molecules are known to exert estr...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e61758
Main Authors: Ajj, Hussein, Chesnel, Amand, Pinel, Sophie, Plenat, François, Flament, Stephane, Dumond, Helene
Format: Article
Language:English
Subjects:
4-tert-Octylphenol
Alkylphenols
Androstadienes - pharmacology
Animals
Automatic
Biology
Bisphenol A
Cancer
Carcinogens, Environmental - pharmacology
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - pathology
Cell growth
Cell proliferation
Cell Proliferation - drug effects
Contamination
Cosmetics
Cyclic AMP response element-binding protein
Cyclic AMP Response Element-Binding Protein - genetics
Cyclic AMP Response Element-Binding Protein - metabolism
Deoxyribonucleic acid
DNA
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA methylation
DNA methyltransferase
DNA microarrays
Engineering Sciences
Environmental monitoring
Epigenesis, Genetic - drug effects
Epigenetic inheritance
Epigenetics
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogen receptors
Estrogens
Etiology
Experiments
Exposure
Gene expression
Gene Expression Regulation, Neoplastic - drug effects
Genes
Household products
Kinases
Life Sciences
Male
Mammals
Medicine
Methylation
Mice
Mice, Nude
Neoplasm Transplantation
Neurotrophin 2
Nonylphenol
Ovarian cancer
Pharmacology
Phenols - pharmacology
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Prostate
Protein Isoforms - genetics
Protein Isoforms - metabolism
Puberty
Receptors
Seminoma
Seminoma - genetics
Seminoma - metabolism
Seminoma - pathology
Signal Transduction
Signaling
Testes
Testicular cancer
Testicular Neoplasms - genetics
Testicular Neoplasms - metabolism
Testicular Neoplasms - pathology
Tumors
Xenografts
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Long chain alkylphenols are man-made compounds still present in industrial and agricultural processes. Their main use is domestic and they are widespread in household products, cleansers and cosmetics, leading to a global environmental and human contamination. These molecules are known to exert estrogen-like activities through binding to classical estrogen receptors. In vitro, they can also interact with the G-protein coupled estrogen receptor. Testicular germ cell tumor etiology and progression are proposed to be stimulated by lifelong estrogeno-mimetic exposure. We studied the transduction signaling pathways through which an alkyphenol mixture triggers testicular cancer cell proliferation in vitro and in vivo. Proliferation assays were monitored after exposure to a realistic mixture of 4-tert-octylphenol and 4-nonylphenol of either TCam-2 seminoma derived cells, NT2/D1 embryonal carcinoma cells or testis tumor in xenografted nude mice. Specific pharmacological inhibitors and gene-silencing strategies were used in TCam-2 cells in order to demonstrate that the alkylphenol mix triggers CREB-phosphorylation through a rapid, ERα36-PI3kinase non genomic pathway. Microarray analysis of the mixture target genes revealed that this pathway can modulate the expression of the DNA-methyltransferase-3 (Dnmt3) gene family which is involved in DNA methylation control. Our results highlight a key role for ERα36 in alkylphenol non genomic signaling in testicular germ cell tumors. Hence, ERα36-dependent control of the epigenetic status opens the way for the understanding of the link between endocrine disruptor exposure and the burden of hormone sensitive cancers.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0061758