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Vol. 9, No. 1-2, 2009
Issue release date: April 2009
Section title: Original Paper
Pancreatology 2009;9:136–144
(DOI:10.1159/000178884)

ATP-Binding Cassette C Transporters in Human Pancreatic Carcinoma Cell Lines

Upregulation in 5-Fluorouracil-Resistant Cells

Hagmann W. · Jesenofsky R. · Faissner R. · Guo C. · Löhr J.M.
aClinical Cooperation Unit of Molecular Gastroenterology, German Cancer Research Center, Heidelberg, Germany; bDepartment of Surgical Gastroenterology, CLINTEC, Karolinska Institute, Stockholm, Sweden

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 2/15/2008
Accepted: 7/1/2008
Published online: 12/13/2008

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 0

ISSN: 1424-3903 (Print)
eISSN: 1424-3911 (Online)

For additional information: http://www.karger.com/PAN

Abstract

Background: Pancreatic cancer is characterized by high resistance to chemotherapy. Such chemoresistance can be mediated by multidrug resistance proteins (MRPs), breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein. However, the contribution of individual MRP isoforms to chemoresistance in pancreatic carcinoma is unclear. We studied ATP-binding cassette (ABC) transporter expression in human pancreatic carcinoma cell lines as compared to primary pancreatic duct cells, and analyzed the MRP expression profile in 5-fluorouracil-resistant cells. Methods: Transporter expression was analyzed by quantitative and qualitative RT-PCR, by immunoblot, and chemoresistance by cytotoxicity assay. Results: Primary pancreatic duct cells expressed MRP1, MRP3, MRP4, and MRP5, but not MRP2 mRNA. The established carcinoma cell lines expressed MRP1, MRP4, and MRP5, most of them also MRP2, MRP3, MRP7, and BCRP, but none contained detectable amounts of MRP6, MRP8, or MRP9 mRNA. Immunoblot analyses demonstrated presence of MRP1, MRP4, and MRP5 protein in all, but MRP3 and BCRP protein only in some of these cells. Compared to parental Capan-1 cells, Capan-1 cells with acquired chemoresistance towards 5-fluorouracil showed an upregulated mRNA and protein expression of MRP3, MRP4, and MRP5. In addition, silencing of MRP5 by RNA interference resulted in enhanced sensitivity of parental Capan-1 cells towards 5-fluorouracil cytotoxicity. Conclusion: MRP3, MRP4, and MRP5 are upregulated in 5-fluorouracil-resistant cells, and MRP5 contributes to 5-FU resistance in pancreatic carcinoma cells.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 2/15/2008
Accepted: 7/1/2008
Published online: 12/13/2008

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 0

ISSN: 1424-3903 (Print)
eISSN: 1424-3911 (Online)

For additional information: http://www.karger.com/PAN


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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