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Regulation of DNA damage tolerance by the AhR pathway and its role in glioma progression
Author(s) -
Bostian April,
Eoff Robert
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.976.4
Subject(s) - dna damage , aryl hydrocarbon receptor , glioma , biology , cancer research , dna , polymerase , dna repair , dna polymerase , signal transduction , microbiology and biotechnology , genetics , gene , transcription factor
Gliomas, tumors arising in glial cells in the brain, are associated with a particularly poor patient prognosis. These tumors generally exhibit little response to chemotherapy and radiation treatments and have constitutive and marked DNA damage response activation even before the onset of treatment. This study's objective is to examine glioma‐specific activation of the aryl hydrocarbon receptor (AhR) pathway and the subsequent effect upon DNA damage tolerance mechanisms, especially on the regulation of the Y‐family polymerases and the effect of their up‐regulation on mutagenic bypass of DNA adducts. The hypothesis that the AhR signaling pathway transcriptionally regulates levels of two members of this family, human polymerase kappa (hpol κ) and human polymerase iota (hpol κ), was tested using in vitro cell culture assays after exposure to AhR agonists. Initial luciferase reporter assays and immunoblotting results suggest hpol κ may indeed be up‐regulated by this pathway in gliomas. Results from this study will contribute to our understanding of how DNA damage tolerance affects glioma development and may provide insight into the mechanisms leading to the chemoresistance often inherent in this disease. Supported in part by USPHS R00 GM084460 (R.L.E.).