PMID- 19020751
OWN - NLM
STAT- MEDLINE
DCOM- 20090202
LR  - 20211203
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 33
IP  - 6
DP  - 2008 Dec
TI  - Expression of multidrug resistance-associated protein 2 is involved in 
      chemotherapy resistance in human pancreatic cancer.
PG  - 1187-94
AB  - Despite the recent introduction of the new anticancer agents gemcitabine (GEM) 
      and TS-1, as well as combination regimens such as GEM plus cisplatin (CDDP), 
      pancreatic cancer treatment remains relatively ineffective. Both intrinsic and 
      acquired resistance to chemotherapy are major roadblocks to the successful 
      treatment of pancreatic cancer patients. The aims of this study were to examine 
      the expression of multidrug resistance-associated proteins (MRPs) MRP1, MRP2 and 
      MRP3 and to evaluate the correlation between MRP2 expression and CDDP resistance 
      in human pancreatic cancer. Five human pancreatic cancer cell lines and several 
      surgically resected pancreatic cancer tissues were subjected to 
      reverse-transcriptase (RT)-PCR, real-time PCR and immunohistochemical analysis. 
      While MRP1 and MRP2 mRNA was expressed in all cell lines, MRP3 mRNA was only 
      detected in two cell lines. In resected pancreatic cancer tissues, only MRP2 mRNA 
      was expressed and it was overexpressed compared with normal pancreatic tissues. 
      MRP2 protein expression was observed in 77.5% (31/40) of cancer tissues, 
      primarily in the cytoplasm of cancer cells, but was not observed in normal 
      pancreatic tissue. Two CDDP-resistant pancreatic cancer cell line SUIT-2 
      variants, SUIT-2-CD3 and SUIT-2-CD4, were established by continuously 
      administering 10 nM CDDP to SUIT-2 cell lines for 3 and 4 months, respectively. 
      Incubation of these cells with CDDP in the presence of anti-MRP2 antibody or the 
      MRP2 inhibitor MK-571 in a growth inhibition assay demonstrated that the 
      CDDP-resistant variants were more resistant to CDDP than the parent cell line and 
      this resistance was diminished by either anti-MRP2 antibody or MK-571. Moreover, 
      RT-PCR and real-time PCR revealed that while induction of MRP2 mRNA expression 
      was increased in CDDP-resistant compared with parent cells, MRP1 and MRP3 
      expression remained unchanged. These observations suggest that MRP2 may correlate 
      to intrinsic and acquired resistance for CDDP in human pancreatic cancer.
FAU - Noma, Bunjiro
AU  - Noma B
AD  - Department of Medicine and Molecular Science, Hiroshima University Graduate 
      School of Biomedical Sciences, Minami-ku, Hiroshima 734-8551, Japan. 
      bunjiro@hiroshima-u.ac.jp
FAU - Sasaki, Tamito
AU  - Sasaki T
FAU - Fujimoto, Yoshifumi
AU  - Fujimoto Y
FAU - Serikawa, Masahiro
AU  - Serikawa M
FAU - Kobayashi, Kenso
AU  - Kobayashi K
FAU - Inoue, Motoki
AU  - Inoue M
FAU - Itsuki, Hiroshi
AU  - Itsuki H
FAU - Kamigaki, Michihiro
AU  - Kamigaki M
FAU - Minami, Tomoyuki
AU  - Minami T
FAU - Chayama, Kazuaki
AU  - Chayama K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (ABCC2 protein, human)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Multidrug Resistance-Associated Protein 2)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Propionates)
RN  - 0 (Quinolines)
RN  - 0 (RNA, Messenger)
RN  - 1YV0492L5Z (multidrug resistance-associated protein 3)
RN  - 5Q9O54P0H7 (verlukast)
RN  - Q20Q21Q62J (Cisplatin)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cisplatin/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - *Drug Resistance, Neoplasm/drug effects/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Multidrug Resistance-Associated Protein 2
MH  - Multidrug Resistance-Associated Proteins/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Pancreatic Neoplasms/drug therapy/genetics/*metabolism/pathology
MH  - Propionates/pharmacology
MH  - Quinolines/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Up-Regulation
EDAT- 2008/11/21 09:00
MHDA- 2009/02/03 09:00
CRDT- 2008/11/21 09:00
PHST- 2008/11/21 09:00 [pubmed]
PHST- 2009/02/03 09:00 [medline]
PHST- 2008/11/21 09:00 [entrez]
PST - ppublish
SO  - Int J Oncol. 2008 Dec;33(6):1187-94.