Transforming growth factor-β pathway:: Role in pancreas development and pancreatic disease

被引:70
作者
Rane, SG [1 ]
Lee, JH [1 ]
Lin, HM [1 ]
机构
[1] NCI, Lab Cell Regulat & Carcinogenesis, Cell Cycle & Human Dis Grp, NIH, Bethesda, MD 20892 USA
关键词
TGF-beta; Smad4 (DPC4); pancreas; pancreatic cancer; diabetes;
D O I
10.1016/j.cytogfr.2005.09.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
The pancreas is a complex exocrine and endocrine gland that controls many homeostatic functions. The exocrine pancreas produces and secretes digestive enzymes, whereas, the endocrine pancreas produces four distinct hormones, chief among them being the glucose regulating hormone-insulin. Diabetes, pancreatitis and pancreatic cancer are some of the main afflictions that result from pancreas dysfunction. Transforming growth factor-beta (TGF-beta) proteins are central regulators of pancreas cell function, and have key roles in pancreas development and pancreatic disease. Since expression levels and kinase activities of components of TGF-beta signaling are aberrantly altered in diseases of the pancreas, modulating the activity of TGF-beta provides a unique and rational opportunity for therapeutic intervention. Although TGF-beta still remains elusive in terms of our understanding of its multifunctional modes of action, research is moving closer to the design of approaches directed toward modulating its activities for therapeutic benefit. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:107 / 119
页数:13
相关论文
共 120 条
[1]
Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma [J].
Aguirre, AJ ;
Bardeesy, N ;
Sinha, M ;
Lopez, L ;
Tuveson, DA ;
Horner, J ;
Redston, MS ;
DePinho, RA .
GENES & DEVELOPMENT, 2003, 17 (24) :3112-3126
[2]
TGF-β signaling in cancer -: a double-edged sword [J].
Akhurst, RJ ;
Derynck, R .
TRENDS IN CELL BIOLOGY, 2001, 11 (11) :S44-S51
[3]
Albanese C, 1999, J PEDIATR SURG, V34, P693
[4]
Activins as regulators of branching morphogenesis [J].
Ball, EMA ;
Risbridger, GP .
DEVELOPMENTAL BIOLOGY, 2001, 238 (01) :1-12
[5]
Pancreatic cancer biology and genetics [J].
Bardeesy, N ;
DePinho, RA .
NATURE REVIEWS CANCER, 2002, 2 (12) :897-909
[6]
The genetics of the NOD mouse [J].
Baxter, AG ;
Cooke, A .
DIABETES-METABOLISM REVIEWS, 1995, 11 (04) :315-335
[7]
Diabetes mellitus and genetically programmed defects in β-cell function [J].
Bell, GI ;
Polonsky, KS .
NATURE, 2001, 414 (6865) :788-791
[8]
The pancreatic ductal epithelium serves as a potential pool of progenitor cells [J].
Bonner-Weir, S ;
Toschi, E ;
Inada, A ;
Reitz, P ;
Fonseca, SY ;
Aye, T ;
Sharma, A .
PEDIATRIC DIABETES, 2004, 5 :16-22
[9]
Pancreatic stem cells [J].
Bonner-Weir, S ;
Sharma, A .
JOURNAL OF PATHOLOGY, 2002, 197 (04) :519-526
[10]
Expression of a dominant-negative mutant TGF-beta type II receptor in transgenic mice reveals essential roles for TGF-beta in regulation of growth and differentiation in the exocrine pancreas [J].
Bottinger, EP ;
Jakubczak, JL ;
Roberts, ISD ;
Mumy, M ;
Hemmati, P ;
Bagnall, K ;
Merlino, G ;
Wakefield, LM .
EMBO JOURNAL, 1997, 16 (10) :2621-2633