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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

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

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