MDR1/P-glycoprotein and MRP-1 drug efflux pumps in pancreatic carcinoma.
BACKGROUND
Pancreatic cancer is one of the most challenging solid organ malignancies. This is due to its aggressiveness, frequent late presentation as advanced disease and chemoresistance. A better understanding of the molecular basis of its drug resistance is needed.


METHODS
In this study, the first of its kind, the expression of both MDR1 P-gp and MRP-1 protein in pancreatic tumour specimens was examined by immunohistochemistry. Expression of these drug efflux pumps was examined using semi-quantitative immunohistochemistry according to the percentage of cells within the tumour, demonstrating another staining intencity.


RESULTS
Overall, 93.3% of pancreatic carcinomas expressed MDR1 P-gp, approximately 31% co-expressed MRP-1 with MDR1 P-gp, while 6.7% expressed neither of these proteins.


CONCLUSIONS
Our results show that drug efflux pumps, in particular that of MDR1 P-gp, are frequently expressed in pancreatic cancer. While a causative role for these efflux pumps in pancreatic cancer chemoresistance cannot necessarily be concluded, the information presented here should be considered when selecting chemotherapy/drug efflux pump inhibitors for future therapies.
O'Driscoll
L
L
National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland. Lorraine.ODriscoll@dcu.ie
Walsh
N
N
Larkin
A
A
Ballot
J
J
Ooi
W S
WS
Gullo
G
G
O'Connor
R
R
Clynes
M
M
Crown
J
J
Kennedy
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1