Repair gene O 6 ‐methylguanine‐DNA methyltransferase is controlled by SP1 and up‐regulated by glucocorticoids, but not by temozolomide and radiation

• Published in: Journal of neurochemistry Vol. 144; no. 2; pp. 139 - 151
• Main Authors: Aasland, Dorthe, Reich, Thomas R., Tomicic, Maja T., Switzeny, Olivier J., Kaina, Bernd, Christmann, Markus
• Format: Journal Article
• Language: English
• Published: England 01.01.2018
• Subjects: Antineoplastic Agents, Alkylating - pharmacology; Dexamethasone - pharmacology; DNA Repair Enzymes - drug effects; DNA Repair Enzymes - genetics; DNA Repair Enzymes - radiation effects; Enzyme Induction - drug effects; Enzyme Induction - radiation effects; Gene Knockdown Techniques; Glucocorticoids - pharmacology; Humans; O-Methylguanine-DNA Methyltransferase - drug effects; O-Methylguanine-DNA Methyltransferase - genetics; O-Methylguanine-DNA Methyltransferase - radiation effects; Promoter Regions, Genetic - genetics; RNA, Messenger - pharmacology; Sp1 Transcription Factor - drug effects; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - radiation effects; Temozolomide - pharmacology; Up-Regulation - drug effects; Up-Regulation - radiation effects; temozolomide; glioblastoma; MGMT; transcriptional regulation; ionizing radiation

Therapy of malignant glioma relies on treatment with the O -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences, DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O -alkylguanine...