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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenal Gland Neoplasms / genetics
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Adrenal Gland Neoplasms / pathology
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Aged
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Antibodies, Monoclonal / immunology
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Autoreceptors / drug effects
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Autoreceptors / immunology
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Autoreceptors / physiology
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Carcinoid Tumor / genetics
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Carcinoid Tumor / secondary
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Carcinoma, Medullary / genetics
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Carcinoma, Medullary / pathology
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Cell Division / drug effects
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DNA, Neoplasm / genetics
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ErbB Receptors / biosynthesis*
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ErbB Receptors / drug effects
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ErbB Receptors / genetics
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ErbB Receptors / immunology
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ErbB Receptors / physiology
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Liver Neoplasms / genetics
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Liver Neoplasms / secondary
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Lymphatic Metastasis
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Male
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Middle Aged
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Neoplasm Proteins / biosynthesis*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Neuroendocrine Tumors / genetics*
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Neuroendocrine Tumors / pathology
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Paraganglioma / genetics
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Paraganglioma / pathology
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Pheochromocytoma / genetics
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Pheochromocytoma / pathology
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RNA, Messenger / analysis
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RNA, Neoplasm / analysis
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Retroperitoneal Neoplasms / genetics
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Retroperitoneal Neoplasms / pathology
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Thyroid Neoplasms / genetics
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Thyroid Neoplasms / pathology
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Transforming Growth Factor alpha / biosynthesis*
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Transforming Growth Factor alpha / genetics
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Transforming Growth Factor alpha / pharmacology
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Transforming Growth Factor alpha / physiology
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
Substances
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Antibodies, Monoclonal
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Autoreceptors
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DNA, Neoplasm
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Transforming Growth Factor alpha
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ErbB Receptors