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Expression of transforming growth factor alpha and its receptor in human neuroendocrine tumours.

Journal article
Authors Ola Nilsson
Bo Wängberg
Lars Kölby
G S Schultz
Håkan Ahlman
Published in International journal of cancer. Journal international du cancer
Volume 60
Issue 5
Pages 645-51
ISSN 0020-7136
Publication year 1995
Published at Institute of Surgical Sciences, Department of Surgery
Pages 645-51
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adrenal Gland Neoplasms, genetics, pathology, Aged, Antibodies, Monoclonal, immunology, Autoreceptors, drug effects, immunology, physiology, Carcinoid Tumor, genetics, secondary, Carcinoma, Medullary, genetics, pathology, Cell Division, drug effects, DNA, Neoplasm, genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms, genetics, secondary, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Proteins, biosynthesis, genetics, physiology, Neuroendocrine Tumors, genetics, pathology, Paraganglioma, genetics, pathology, Pheochromocytoma, genetics, pathology, RNA, Messenger, analysis, RNA, Neoplasm, analysis, Receptor, Epidermal Growth Factor, biosynthesis, drug effects, genetics, immunology, physiology, Retroperitoneal Neoplasms, genetics, pathology, Thyroid Neoplasms, genetics, pathology, Transforming Growth Factor alpha, biosynthesis, genetics, pharmacology, physiology, Tumor Cells, Cultured, drug effects, secretion
Subject categories Cancer and Oncology, Gastroenterology and Hepatology

Abstract

Transforming growth-factor-alpha (TGF-alpha) is a 50-amino-acid polypeptide that binds to the epidermal growth factor (EGF) receptor and stimulates cell growth. It has been suggested that enhanced production of TGF-alpha and EGF receptors by tumour cells promote tumour-cell growth by autocrine mechanisms. In the present study we have investigated the expression of TGF-alpha and EGF receptors in human neuroendocrine tumours, including midgut carcinoid tumours, phaeochromocytomas and medullary thyroid carcinomas. TGF-alpha expression was demonstrated in biopsies of all tumours examined (n = 30) and EGF receptors in a majority of tumours by Northern analysis and/or immunocytochemistry. Expression of TGF-alpha and EGF receptors was also demonstrated in primary cultures of tumour cells. Carcinoid tumours and phaeochromocytomas in culture secreted detectable amounts of TGF-alpha into the culture medium (400-700 pM). The amount of secreted TGF-alpha could be suppressed by octreotide treatment in individual tumours. Administration of exogenous TGF-alpha stimulated carcinoid tumour growth in vitro as determined by the DNA contents of cell cultures. The growth-stimulatory effect of TGF-alpha could be partially blocked by the use of neutralizing anti-EGF receptor monoclonal antibodies (MAbs). In conclusion, several human neuroendocrine tumours express both TGF-alpha and EGF receptors in in vivo and in vitro, suggesting that TGF-alpha may regulate tumour-cell growth by autocrine mechanisms.

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