NDLI: Ligand-independent activation of the arylhydrocarbon receptor by ETK (Bmx) tyrosine kinase helps MCF10AT1 breast cancer cells to survive in an apoptosis-inducing environment.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fujisawa, Yasuko Li, Wen Wu, Dalei Wong, Patrick Vogel, Christoph Dong, Bin Kung, Hsing-Jien Matsumura, Fumio
Description	Country affiliation: United States Author Affiliation: Fujisawa Y ( Department of Environmental Toxicology, University of California Davis, One Shields Avenue, Davis, CA 95616, USA.)
Abstract	It has been reported that the arylhydrocarbon receptor (AHR) is overexpressed in certain types of breast tumors. However, so far no concrete evidence has been provided yet as to why and how the overexpressed AHR in those cancer cells is functionally activated without exogenous ligands. Here we show that the AHR was functionally activated when estrogen receptor-negative, AHR overexpressing MCF10AT1 human breast cancer cells (designated P20E) were subjected to serum starvation. Transfection of cells with ETK-KQ, a plasmid for kinase-dead epithelial and endothelial tyrosine kinase (ETK), attenuated this AHR activation. Artificial over-expression of ETK in P20E cells through transfection with wild-type ETK plasmid (ETK-wt) caused up-regulation of cytochrome P4501a1 (CYP1A1; a marker of functional activation of AHR). Furthermore, ablation of ETK expression by a specific antisense oligonucleotide or AG879, a specific inhibitor of ETK kinase suppressed activation of AHR induced by omeprazole, a strong ligand-independent activator of AHR. Activation of ETK in those cells conferred them resistance to UVB- as well as doxorubicin-induced apoptosis, both of which were reversed by ETK-KQ. Together, these findings support our conclusion that ETK is the tyrosine kinase responsible for the functional activation of the AHR in these mammary epithelial cells.
File Format	HTM / HTML
ISSN	14316730
Issue Number	10
Volume Number	392
e-ISSN	14374315
Journal	Biological Chemistry
Language	English
Publisher	Walter de Gruyter
Publisher Date	2011-10-01
Publisher Place	Germany
Access Restriction	Subscribed
Subject Keyword	Discipline Biochemistry Apoptosis Drug Effects Breast Neoplasms Enzymology Protein-tyrosine Kinases Metabolism Receptors, Aryl Hydrocarbon Antibiotics, Antineoplastic Pharmacology Radiation Effects Drug Therapy Genetics Cell Line, Tumor Cell Survival Cytochrome P-450 Cyp1a1 Doxorubicin Drug Resistance, Neoplasm Enzyme Activation Female Gene Expression Regulation, Neoplastic Humans Transfection Journal Article
Content Type	Text
Resource Type	Article
Subject	Clinical Biochemistry Biochemistry Molecular Biology

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