Up-regulation of DDX39 in human pancreatic cancer cells with acquired gemcitabine resistance compared to gemcitabine-sensitive parental cells.

Abstract

Intrinsic or acquired resistance of pancreatic cancer to gemcitabine (2'-deoxy-2'-difluorodeoxycytidine) is an important factor in the failure of gemcitabine treatment. Proteomic analysis of gemcitabine-sensitive KLM1 pancreatic cancer cells and -resistant KLM1-R cells identified heat-shock protein-27(HSP27) as a biomarker protein which is involved in gemcitabine resistance. However, a knock-down experiment showed that HSP27 was not the only protein implicated with gemcitabine-resistance. Finding further candidate proteins is necessary for achieving effective gemcitabine therapy for patients with pancreatic cancer. DDX39 is an Asp-Glu-Ala-Asp (DEAD)-box RNA helicase reported to be overexpressed in tumor cells, such as lung squamous cell cancer, gastrointestinal stromal tumor, urinary bladder cancer and malignant pleural mesothelioma. In urinary bladder cancer cells, overexpression of this protein is intimately bound with tumorigenesis and poor prognosis. In the present study, the expression of DDX39 in gemcitabine-sensitive KLM1 and -resistant KLM1-R cells was compared. It was found that DDX39 was significantly up-regulated in gemcitabine-resistant KLM1-R cells compared to sensitive KLM1 cells. The ratio of expression of DDX39 to that of actin was significantly up-regulated in KLM1-R cells compared to KLM1 cells (p=0.0072 by Student's t-test). These results suggest that DDX39 is a possible candidate biomarker for predicting the response of patients with pancreatic cancer to treatment with gemcitabine.

• Authors: Yasuhiro Kuramitsu, Shigeyuki Suenaga, Yufeng Wang, Kazuhiro Tokuda, Takao Kitagawa, Toshiyuki Tanaka, Junko Akada, Shin-Ichiro Maehara, Yoshihiko Maehara, Kazuyuki Nakamura
• Journal: Anticancer research (Anticancer Res) Vol. 33 Issue 8 Pg. 3133-6 (Aug 2013) ISSN: 1791-7530 [Electronic] Greece
• PMID: 23898070 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Deoxycytidine
• DDX39A protein, human
• DEAD-box RNA Helicases
• Gemcitabine

Topics

• Blotting, Western
• Cell Line, Tumor
• DEAD-box RNA Helicases (metabolism)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Pancreatic Neoplasms (metabolism)
• Up-Regulation (drug effects)
• Gemcitabine