Thymosin Beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation.
BACKGROUND
Thymosin beta 4 (T beta 4) has been shown to be associated with tumor metastasis and angiogenesis; however, its role in pancreatic cancer has not been understood. In the current study, we examined the expression of T beta 4 in pancreatic cancer cells, and determined the effect of exogenous T beta 4 on cytokine secretion, and signal transduction in human pancreatic cancer cells.


RESULTS
Pancreatic cancer cell lines expressed higher amount of T beta 4 mRNA than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous T beta 4 increased the secretion of proinflammatory cytokines IL-6, IL-8 and MCP-1 in Panc-1 cells. In addition, T beta 4 activated Jun N-terminal Kinase (JNK) signaling pathways in pancreatic cancer cells.


METHODS
The mRNA levels of T beta 4 were determined by real-time RT PCR. Phosphorylation of JNK in pancreatic cancer cells was determined using Bio-Plex phosphoprotein assay. The expression of cytokines in human pancreatic cancer cell lines was determined with Bio-Plex cytokine assay.


CONCLUSIONS
T beta 4 might be involved in stimulating human pancreatic cancer progression by promoting proinflammatory cytokine environment and activating JNK signaling pathway. Targeting T beta 4 and related molecules may be a novel therapeutic strategy for pancreatic cancer.
Zhang
Yuqing
Y
Molecular Surgeon Research Center, Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Feurino
Louis W
LW
Zhai
Qihui
Q
Wang
Hao
H
Fisher
William E
WE
Chen
Changyi
C
Yao
Qizhi
Q
Li
Min
M
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007700:Kinetics; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D010766:Phosphorylation; D013947:Thymosin / Q000235:genetics*; D000099201:Thymosin beta(4)
D016207:Cytokines; D048670:MAP Kinase Kinase 4; D013947:Thymosin; D000099201:Thymosin beta(4)