Oncotarget

Research Papers:

Reduction of MLH1 and PMS2 confers temozolomide resistance and is associated with recurrence of glioblastoma

Yoshinari Shinsato, Tatsuhiko Furukawa _, Shunji Yunoue, Hajime Yonezawa, Kentarou Minami, Yukihiko Nishizawa, Ryuji Ikeda, Kohichi Kawahara, Masatatsu Yamamoto, Hirofumi Hirano, Hiroshi Tokimura and Kazunori Arita

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2013; 4:2261-2270. https://doi.org/10.18632/oncotarget.1302

Metrics: PDF 3581 views  |   HTML 5504 views  |   ?  


Abstract

Yoshinari Shinsato1,2, Tatsuhiko Furukawa2, Shunji Yunoue1, Hajime Yonezawa1, Kentarou Minami2,3, Yukihiko Nishizawa2,3, Ryuji Ikeda3, Kohichi Kawahara2, Masatatsu Yamamoto2, Hirofumi Hirano1, Hiroshi Tokimura1, and Kazunori Arita1

1 Department of Neurosurgery, Graduate School of Medical and Dental Sciences Kagoshima University, Kagoshima, Japan;

2 Department of Molecular Oncology, Graduate School of Medical and Dental Sciences Kagoshima University, Kagoshima, Japan;

3 Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences Kagoshima University, Kagoshima, Japan

Correspondence:

Tatsuhiko Furukawa, email:

Keywords: temozolomide, MLH1, PMS2, MutL-alpha , resistance, recurrence, glioblastoma

Received: August 20, 2013 Accepted: October 12 , 2013 Published: October 14, 2013

Abstract

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 1302