Alternative TitleReduction of MLH1 and PMS2 confers temozolomide resistance and is associated with recurrence of glioblastoma
Degree Type博士(医学)
Doctor of Philosophy in Medical Science
Note (General)博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
Although there is a relationship between DNA repair deficiency and temozolomide (TMZ) resistance in glioblastoma (GBM), it remains unclear which molecule is associated with GBM recurrence. We isolated three TMZ-resistant human GBM cell lines and examined the expression of O6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair (MMR) components. We used immunohistochemical analysis to compare MutL homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2) and MGMT expression in primary and recurrent GBM specimens obtained from GBM patients during TMZ treatment. We found a reduction in MLH1 expression and a subsequent reduction in PMS2 protein levels in TMZ-resistant cells. Furthermore, MLH1 or PMS2 knockdown confered TMZ resistance. In recurrent GBM tumours, the expression of MLH1 and PMS2 was reduced when compared to primary tumours.Yoshinari Shinsato, Tatsuhiko Furukawa, Shunji Yunoue, Hajime Yonezawa, Kentarou Minami, Yukihiko Nishizawa, Ryuji Ikeda, Kohichi Kawahara, Masatatsu Yamamoto, Hirofumi Hirano, Hiroshi Tokimura, and Kazunori AritaReduction of MLH1 and PMS2 confers temozolomide resistance and is associated with recurrence of glioblastomaOncotarget 4(12) 2013doi: https://doi.org/10.18632/oncotarget.1302
DOIinfo:doi/10.18632/oncotarget.1302
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2015-12-01T13:36:39+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション