p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines.
- Author:
Sung Ung MOON
1
;
Jin Won KIM
;
Ji Hea SUNG
;
Mi Hyun KANG
;
Se Hyun KIM
;
Hyun CHANG
;
Jeong Ok LEE
;
Yu Jung KIM
;
Keun Wook LEE
;
Jee Hyun KIM
;
Soo Mee BANG
;
Jong Seok LEE
Author Information
- Publication Type:Original Article
- Keywords: PAK4; hENT1; Gemcitabine; Pancreatic neoplasms
- MeSH: Cell Line*; Cell Proliferation; Cell Survival; Equilibrative Nucleoside Transporter 1; Humans; p21-Activated Kinases; Pancreatic Neoplasms*; Phosphotransferases*; Polymerase Chain Reaction; Reverse Transcription; RNA, Messenger; RNA, Small Interfering; Up-Regulation
- From:Cancer Research and Treatment 2015;47(3):501-508
- CountryRepublic of Korea
- Language:English
- 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.
