Somatostatin receptor subtype mRNA expression in human colorectal cancer

Laws, Siobhan Alison Mary (1999) Somatostatin receptor subtype mRNA expression in human colorectal cancer. University of Southampton, Doctoral Thesis.

Abstract

Cancer of the gastrointestinal tract is a common cause of cancer related mortality and morbidity.

Manipulation of the cellular response to native peptides provides the basis for the development of alternative treatment strategies. This thesis investigates the cellular basis for using the growth inhibitory peptide somatostatin for the treatment of advanced gastrointestinal malignancies.

The somatostatin receptor is the key to predicting the effect of somatostatin or its analogues in cancer therapy. This thesis determines the distribution of the somatostatin receptor subtypes in human colorectal cancer primary tumours, metastases and normal mucosa using the molecular methods of reverse-transcription polymerase chain reaction and in situ hybridisation. In situ hybridisation has not previously been used to study the human colon and our protocol differs from (and is probably superior to) the standard.

The results indicate near ubiquitous expression of somatostatin receptor subtype 2 throughout normal and malignant epithelia plus dense stromal staining. Although expression is universal, treatment with somatostatin analogues is well tolerated and there may still be a role for the use of somatostatin analogues in metastatic disease. Receptor subtype 5 is expressed by significantly fewer advanced tumours and metastases and may have a role as a tumour supressor. Receptor subtypes 1, 3 and 4 are expressed infrequently in no discernible pattern. The project adds to available information on tissue distribution of somatostatin receptor subtypes.

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