Role of gastrin peptides in carcinogenesis.
Gastrin gene expression is upregulated in a number of pre-malignant conditions and established cancer through a variety of mechanisms. Depending on the tissue where it is expressed and the level of expression, differential processing of the polypeptide product leads to the production of different biologically active peptides. In turn, acting through the classical CCK-2R receptor, CCK-2R isoforms and alternative receptors, these peptides trigger signalling pathways which influence the expression of downstream genes that affect cell survival, angiogenesis and invasion. Here we review this network of events, highlighting the importance of cellular context for interpreting the role of gastrin peptides and a possible role for gastrin in supporting the early stage of carcinogenesis.
Grabowska
Anna M
AM
Division of Pre-Clinical Oncology, D Floor, West Block, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, UK. anna.grabowska@nottingham.ac.uk
Watson
Susan A
SA
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D003576:Electron Transport Complex IV / Q000378:metabolism; D005755:Gastrins / Q000737:chemistry* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry*
D005755:Gastrins; D010455:Peptides; D003576:Electron Transport Complex IV; D020782:Matrix Metalloproteinases