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

Yasuko Fujisawa, Wen Li, Dalei Wu, Patrick Wong, Christoph Vogel, Bin Dong, Hsing Jien Kung, Fumio Matsumura

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)897-908
Number of pages12
JournalBiological Chemistry
Volume392
Issue number10
DOIs
Publication statusPublished - Oct 1 2011
Externally publishedYes

Fingerprint

Receptor Protein-Tyrosine Kinases
Protein-Tyrosine Kinases
Chemical activation
Cells
Apoptosis
Breast Neoplasms
Ligands
Transfection
Plasmids
Phosphotransferases
Cytochrome P-450 CYP1A1
Omeprazole
Antisense Oligonucleotides
Cytochromes
Starvation
Ablation
Estrogen Receptors
Doxorubicin
Tumors
Breast

Keywords

  • arylhydrocarbon receptor
  • breast cancer
  • endothelial tyrosine kinase
  • ligand-independent activation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Ligand-independent activation of the arylhydrocarbon receptor by ETK (Bmx) tyrosine kinase helps MCF10AT1 breast cancer cells to survive in an apoptosis-inducing environment. / Fujisawa, Yasuko; Li, Wen; Wu, Dalei; Wong, Patrick; Vogel, Christoph; Dong, Bin; Kung, Hsing Jien; Matsumura, Fumio.

In: Biological Chemistry, Vol. 392, No. 10, 01.10.2011, p. 897-908.

Research output: Contribution to journalArticle

Fujisawa, Yasuko ; Li, Wen ; Wu, Dalei ; Wong, Patrick ; Vogel, Christoph ; Dong, Bin ; Kung, Hsing Jien ; Matsumura, Fumio. / Ligand-independent activation of the arylhydrocarbon receptor by ETK (Bmx) tyrosine kinase helps MCF10AT1 breast cancer cells to survive in an apoptosis-inducing environment. In: Biological Chemistry. 2011 ; Vol. 392, No. 10. pp. 897-908.
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