Back to Search
Start Over
p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines
- Source :
- Cancer Research and Treatment : Official Journal of Korean Cancer Association
- Publication Year :
- 2014
- Publisher :
- Korean Cancer Association, 2014.
-
Abstract
- Purpose p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets. Materials and methods Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA. Results Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine. Conclusion PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer.
- Subjects :
- Cancer Research
Gene knockdown
Predictive marker
Pancreatic neoplasms
endocrine system diseases
biology
business.industry
Cell growth
Kinase
Equilibrative nucleoside transporter 1
Bioinformatics
medicine.disease
hENT1
Gemcitabine
Reverse transcription polymerase chain reaction
Oncology
PAK4
Pancreatic cancer
biology.protein
Cancer research
Medicine
Original Article
business
medicine.drug
Subjects
Details
- ISSN :
- 20059256 and 15982998
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Cancer Research and Treatment
- Accession number :
- edsair.doi.dedup.....b7e0acf6bae7f9049ebfda6d832fb200