[Down-regulated expression of PP2A catalytic subunit in pancreatic cancer cells promotes cell growth].
OBJECTIVE
To investigate the expression of protein phosphatase 2A catalytic subunit (PP2Ac) in pancreatic cancer and the regulation of this gene on JNK/c-Jun/AP-1 pathway and cell growth.


METHODS
Expression of PP2Ac was determined by real-time PCR. Cell viability was tested by MTT.Expression and phosphorylation levels of proteins were detected by Western blotting. Cell cycle was assayed by flow cytometry. Transcription activity was measured by luciferase reporter gene assay.


RESULTS
Suppressed PP2Ac expression was detected in pancreatic cancer tissues. PP2Ac expression in the pancreatic cancer cell lines was also at a low level.Overexpression of the two isoforms of PP2Ac, PP2Acα and PP2Acβ, in pancreatic cancer cells repressed cell growth. Cell viability decreased (33.89 ± 2.05)% (t = 28.607, P < 0.001) and (16.66 ± 2.81)% (t = 10.257, P = 0.001) respectively 72 hours after transfection.Overexpression of PP2Acα and PP2Acβ down-regulated the phosphorylation levels of JNK and c-Jun, and made the transcriptional activity of AP-1 decrease (47.18 ± 2.28)% (t = 11.230, P < 0.001) and (30.89 ± 8.09)% (t = 6.612, P = 0.003) respectively, indicating the down-regulation of PP2Ac up-regulated the activity of JNK/c-Jun/AP-1 pathway. Blocking the JNK pathway using a selective inhibitor, SP600125, induced G2/M cell cycle arrest and repressed cell proliferation. Cell viability decreased (31.38 ± 1.33)% (t = 40.930, P < 0.001) after treatment with JNK inhibitor for 72 hours.


CONCLUSIONS
Suppressed expression of PP2Ac in pancreatic cancer facilitated cell growth through up-regulating the activity of JNK/c-Jun/AP-1 pathway.
Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Wei
W
Li
Feiran
F
Gong
Zheng
Z
Chen
Yang
Y
Zong
Kai
K
Chen
Daoming
D
Li
Min
M
Tao
Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029, China. Email:xuzekuan@njmu.edu.cn.
Zekuan
Z
Xu
D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D054648:Protein Phosphatase 2 / Q000378:metabolism*
D048031:JNK Mitogen-Activated Protein Kinases; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2