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Gastrin, gastrin receptors and colorectal carcinoma
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  1. G S BALDWIN,
  2. A SHULKES
  1. Department of Surgery,
  2. A&RMC, Austin Campus,
  3. Locked Bag 25, Heidelberg,
  4. Victoria 3084, Australia
  1. Dr Baldwin (email:gsb{at}austin.unimelb.edu.au).

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The possibility that gastrin may play a role in the development of colorectal carcinoma has aroused considerable interest over the past decade. In early reports some colorectal carcinomas and colorectal carcinoma cell lines were shown to produce gastrin,1 to express gastrin receptors,2 and to respond mitogenically to exogenous gastrin.2 The most favoured explanation for these observations was an autocrine or paracrine loop in which gastrin was produced by the tumour, bound to tumour receptors, and stimulated tumour growth. However, gastrin may also have acted as an endocrine agent as hypergastrinaemia has been reported in a number of patients with colorectal carcinoma, although the source of the gastrin has not been defined.3-5 Further studies of the expression of gastrin6-8 and gastrin receptors9 ,10 in colorectal carcinomas and colorectal carcinoma cell lines, and of hypergastrinaemia in patients with colorectal carcinoma,11-15 indicated that the early positive reports were not universally correct. Recent information on the nature and source of the gastrin produced, and the discovery of novel receptors selective for non-amidated gastrins, makes it timely to reconsider the involvement of progastrin derived peptides in colorectal carcinoma.

Synthesis, storage and secretion of gastrin in colorectal carcinomas

There is now abundant evidence that most colorectal carcinomas synthesise progastrin. Gastrin mRNA has been detected by both polymerase chain reaction and northern hybridisation in colorectal carcinoma cell lines, normal human colonic mucosa and colorectal carcinomas.6 ,16-18 The gastrin mRNA is of low abundance but the major band of 0.7 kilobases is identical in sequence to antral gastrin mRNA.6 ,16 ,17 There is, however, considerable disparity in the literature on the proportion of colorectal carcinomas that contain amidated gastrin (table 1). The variable efficiency of translation and extent of postranslational processing of gastrin in peptide producing tumours20 offers an explanation for some of …

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