Thymosin beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation

被引:51
作者
Zhang, Yuqing [1 ]
Feurino, Louis W. [1 ]
Zhai, Qihui [2 ]
Wang, Hao [1 ]
Fisher, William E. [1 ]
Chen, Changyi [1 ]
Yao, Qizhi [1 ]
Li, Min [1 ]
机构
[1] Baylor Coll Med, Michael E DeBakey Dept Surg, Mol Surgeon Res Ctr, Elkins Pancreas Ctr, Houston, TX 77030 USA
[2] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA
关键词
thymosin beta 4; overexpression; tumor tissue; cytokine; proinflammation; JNK activation; pancreatic cancer;
D O I
10.4161/cbt.7.3.5415
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 realtime 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.
引用
收藏
页码:419 / 423
页数:5
相关论文
共 26 条
[1]   THYMOSIN-BETA-4 IS EXPRESSED IN ROS 17/2.8 OSTEOSARCOMA CELLS IN A REGULATED MANNER [J].
ATKINSON, MJ ;
FREEMAN, MW ;
KRONENBERG, HM .
MOLECULAR ENDOCRINOLOGY, 1990, 4 (01) :69-74
[2]   Role of thymosin β4 in tumor metastasis and angiogenesis [J].
Cha, HJ ;
Jeong, MJ ;
Kleinman, HK .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (22) :1674-1680
[3]   Cytokines in pancreatic carcinoma - Correlation with phenotypic characteristics and prognosis [J].
Ebrahimi, B ;
Tucker, SL ;
Li, DH ;
Abbruzzese, JL ;
Kurzrock, R .
CANCER, 2004, 101 (12) :2727-2736
[4]   Inflammatory mechanisms contributing to pancreatic cancer development [J].
Farrow, B ;
Sugiyama, Y ;
Chen, A ;
Uffort, E ;
Nealon, W ;
Evers, M .
ANNALS OF SURGERY, 2004, 239 (06) :763-769
[5]  
FEURINO LW, 2007, CANC BIOL THER, V6
[6]   Growth factors and cytokines in pancreatic carcinogenesis [J].
Friess, H ;
Guo, XZ ;
Nan, BC ;
Kleeff, Ö ;
Büchler, MW .
CELL AND MOLECULAR BIOLOGY OF PANCREATIC CARCINOMA: RECENT DEVELOPMENTS IN RESEARCH AND EXPERIMENTAL THERAPY, 1999, 880 :110-121
[7]  
Furukawa T, 1996, AM J PATHOL, V148, P1763
[8]   Thymosin β4:: A new molecular target for antitumor strategies [J].
Goldstein, AL .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (22) :1646-1647
[9]   DIFFERENTIAL EXPRESSION OF THYMOSIN GENES IN HUMAN TUMORS AND IN THE DEVELOPING HUMAN KIDNEY [J].
HALL, AK .
INTERNATIONAL JOURNAL OF CANCER, 1991, 48 (05) :672-677
[10]   Immortal human pancreatic duct epithelial cell lines with near normal genotype and phenotype [J].
Hong, OY ;
Mou, LJ ;
Luk, C ;
Liu, N ;
Karaskova, J ;
Squire, J ;
Tsao, MS .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (05) :1623-1631