PMID- 27263778
OWN - NLM
STAT- MEDLINE
DCOM- 20161223
LR  - 20171018
IS  - 0485-1439 (Print)
IS  - 0485-1439 (Linking)
VI  - 57
IP  - 5
DP  - 2016 May
TI  - [Epigenetic regulation of cell adhesion-mediated drug resistance acquisition in 
      multiple myeloma].
PG  - 546-55
LID - 10.11406/rinketsu.57.546 [doi]
AB  - Elucidation of the epigenetic mechanisms underlying drug resistance may greatly 
      contribute to the advancement of cancer therapies. In the present study, we 
      identified trimethylation of histone H3 at lysine-27 (H3K27me3) as a critical 
      histone modification for cell adhesion-mediated drug resistance (CAM-DR), which 
      is the most important form of drug resistance in multiple myeloma. Cell adhesion 
      counteracted drug-induced hypermethylation of H3K27 via inactivating 
      phosphorylation of EZH2, leading to sustained expression of anti-apoptotic genes 
      including IGF1, BCL2 and HIF1A. Inhibition of the IGF-1R/PI3K/Akt pathway 
      reversed CAM-DR by promoting EZH2 dephosphorylation and H3K27 hypermethylation 
      both in vitro and in refractory murine myeloma models. To our knowledge, this is 
      the first demonstration of an epigenetic mechanism underlying CAM-DR and provides 
      a rationale for the inclusion of kinase inhibitors counteracting EZH2 
      phosphorylation in combination chemotherapy aimed at increasing the therapeutic 
      index.
FAU - Furukawa, Yusuke
AU  - Furukawa Y
AD  - Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical 
      University.
FAU - Kikuchi, Jiro
AU  - Kikuchi J
LA  - jpn
PT  - Journal Article
PL  - Japan
TA  - Rinsho Ketsueki
JT  - [Rinsho ketsueki] The Japanese journal of clinical hematology
JID - 2984782R
SB  - IM
MH  - Animals
MH  - *Cell Adhesion
MH  - *Epigenesis, Genetic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Multiple Myeloma/drug therapy/*genetics/metabolism
MH  - Phosphorylation
MH  - Signal Transduction
EDAT- 2016/06/07 06:00
MHDA- 2016/12/24 06:00
CRDT- 2016/06/07 06:00
PHST- 2016/06/07 06:00 [entrez]
PHST- 2016/06/07 06:00 [pubmed]
PHST- 2016/12/24 06:00 [medline]
AID - 10.11406/rinketsu.57.546 [doi]
PST - ppublish
SO  - Rinsho Ketsueki. 2016 May;57(5):546-55. doi: 10.11406/rinketsu.57.546.