Forschungsdatenbank PMU-SQQUID

PMU-Autor/inn/en

Abstract

Recent evidence indicates that growth hormone-releasing hormone (GHRH) functions as a growth factor for gastrointestinal (GI) tumours. The tumourigenic effects of GHRH appear to be mediated by the splice variant 1 (SV-1) of GHRH receptor as well as the full length pituitary type receptor for GHRH (GHRH-R). We examined the protein and mRNA expression of GHRH-R and SV-1 in normal human tissues and tumours of the gastrointestinal (GI-) tract by immunohistochernical staining and reverse transcriptase (RT)-PCR. Squamous cells and squarnous cell carcinoma of the oesophagus were negative for GHRH-R and SV-1, while Barrettxxxs mucosa and adenocarcinomas of the oesophagus showed a strong expression of both receptors. The expression of GHRH-R was absent in normal colonic mucosa other than neuroendocrine cells (NE) and lining epithelium (LE) but strong in tubular adenomas of the colon, while the staining for SV-1 was absent in cells other than NE. However, the expression of both receptors was significantly increased in tubulovillous adenomas and colorectal cancers. No differences were seen in protein levels for both receptors between normal and neoplastic tissues of the stomach, pancreas and liver. Because of low mRNA levels for both receptors in all samples tested, only a qualitative assessment could be made. However, mRNA for GHRH-R and SV-1 showed a near-perfect correlation with the assessment of receptor proteins by immunostaining. Our study shows that in contrast to normal mucosa, transformed mucosa of the oesophagus and the colon expresses GHRH-R and SV-1. This aberrant expression of GHRH-R and SV-1 in oesophageal and colorectal malignancies may provide a molecular target for a therapeutic approach based on GHRH antagonists.

Useful keywords (using NLM MeSH Indexing)

Colon/chemistry*

Colonic Neoplasms/chemistry*

Colonic Neoplasms/drug therapy

Cyclin D1/physiology

Esophageal Neoplasms/chemistry*

Esophageal Neoplasms/drug therapy

Esophagus/chemistry*

Growth Hormone-Releasing Hormone/antagonists*

inhibitors

Humans

Immunohistochemistry

Intestinal Mucosa/chemistry

RNA Splicing

RNA, Messenger/analysis

Receptors, Neuropeptide/analysis*

Receptors, Neuropeptide/chemistry

Receptors, Neuropeptide/genetics

Receptors, Pituitary Hormone-Regulating Hormone/analysis*

Receptors, Pituitary Hormone-Regulating Hormone/chemistry

Receptors, Pituitary Hormone-Regulating Hormone/genetics

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