PMID- 18562081
OWN - NLM
STAT- MEDLINE
DCOM- 20081203
LR  - 20151119
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 36
IP  - 10
DP  - 2008 Oct
TI  - Overexpression of the PSMB5 gene contributes to bortezomib resistance in 
      T-lymphoblastic lymphoma/leukemia cells derived from Jurkat line.
PG  - 1278-84
LID - 10.1016/j.exphem.2008.04.013 [doi]
AB  - OBJECTIVE: To study the mechanism of bortezomib resistance in JurkatB lines 
      derived from T-lymphoblastic lymphoma/leukemia Jurkat line. MATERIALS AND 
      METHODS: Cytotoxicities of popular chemotherapeutic drugs to JurkatB cells were 
      analyzed by trypan blue assay. Functional drug efflux in JurkatB cells was 
      determined by flow cytometry utilizing daunorubicin and the expression of 
      P-glycoprotein (P-gp) was detected by Western blot. mRNA expression levels of 
      proteasome beta5 subunit (PSMB5) were measured by quantitation real-time reverse 
      transcription polymerase chain reaction. In situ hybridization was performed to 
      detect the amplification of PSMB5 gene. The chymotrypsin-like activities were 
      assayed by measuring the release of the fluorescent 7-amido-4-methylcoumarin 
      (AMC) from the substrate N-succinyl-Leu-Leu-Val-Tyr-AMC. Cytogenetic studies were 
      performed using R-banded metaphases and fluorescence in situ hybridization (FISH) 
      analysis. IkappaB-alpha levels were detected by Western blot. RESULTS: No 
      cross-resistance to daunorubicin, adriamycin, vindesine, and etoposide was found 
      in JurkatB cells. No evidence of drug efflux was found in JurkatB cells and the 
      expression of P-gp was negative. The PSMB5 mRNA was overexpressed in highly 
      resistant JurkatB5 and JurkatB1 lines compared with parental Jurkat, 
      corresponding well with the increase of chymotrypsin-like activity and a 
      karyotype of i(14q). Amplification of PSMB5 gene was demonstrated by in situ 
      hybridization and FISH. The decreased IkappaB-alpha level in JurkatB5 cells after 
      bortezomib treatment indicating an upregulation of nuclear factor-kappaB 
      (NF-kappaB) activity. CONCLUSION: The mechanism of bortezomib resistance is 
      different from that of multidrug resistance. Overexpression of PSMB5 is an 
      important mechanism for bortezomib resistance in JurkatB lines. NF-kappaB may 
      play a critical role in evading the apoptotic effects.
FAU - Lu, Shuqing
AU  - Lu S
AD  - Department of Hematology, Changhai Hospital, Second Military Medical University, 
      Shanghai, China.
FAU - Chen, Zhilong
AU  - Chen Z
FAU - Yang, Jianmin
AU  - Yang J
FAU - Chen, Li
AU  - Chen L
FAU - Gong, Shenglan
AU  - Gong S
FAU - Zhou, Hong
AU  - Zhou H
FAU - Guo, Lieping
AU  - Guo L
FAU - Wang, Jianmin
AU  - Wang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080617
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (Pyrazines)
RN  - 0 (Ubiquitin)
RN  - 69G8BD63PP (Bortezomib)
RN  - EC 3.4.21.1 (Chymotrypsin)
RN  - EC 3.4.25.1 (PSMB5 protein, human)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Boronic Acids/*therapeutic use
MH  - Bortezomib
MH  - Cell Survival/drug effects
MH  - Chymotrypsin/drug effects/metabolism
MH  - Drug Resistance, Neoplasm/drug effects/*genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Jurkat Cells
MH  - K562 Cells/drug effects
MH  - Leukemia, T-Cell/drug therapy/genetics
MH  - Lymphoma, T-Cell/drug therapy/genetics
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics
MH  - Proteasome Endopeptidase Complex/drug effects/*genetics/metabolism
MH  - Pyrazines/*therapeutic use
MH  - Ubiquitin/drug effects/metabolism
EDAT- 2008/06/20 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/06/20 09:00
PHST- 2008/02/24 00:00 [received]
PHST- 2008/04/23 00:00 [revised]
PHST- 2008/04/24 00:00 [accepted]
PHST- 2008/06/20 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/06/20 09:00 [entrez]
AID - S0301-472X(08)00184-7 [pii]
AID - 10.1016/j.exphem.2008.04.013 [doi]
PST - ppublish
SO  - Exp Hematol. 2008 Oct;36(10):1278-84. doi: 10.1016/j.exphem.2008.04.013. Epub 
      2008 Jun 17.