transforming-growth-factor-alpha and Pheochromocytoma

This study observed the expression of transforming growth factor-alpha (TGF-alpha) and tumor necrosis factor-alpha (TNF-alpha) in pheochromocytoma (PHEO) tissue and examined their effects on the proliferation and apoptosis of human PHEO cells. The mRNA and protein expressions of TGF-alpha and TNF-alpha were higher in PHEO tissues than in normal adrenal medullary tissues, and their expressions varied with pathological features. TGF-alpha and TNF-alpha stimulated the proliferation of primary human PHEO cells, but had no effect on the cell apoptosis. Both TGF-alpha and TNF-alpha might be involved in the pathogenesis of human PHEO. TNF-alpha needs to be further investigated before its treatment of PHEO can be realized in clinical practice.

Topics: Adrenal Gland Neoplasms; Apoptosis; Cell Proliferation; Humans; Immunohistochemistry; Pheochromocytoma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transforming Growth Factor alpha; Tumor Necrosis Factor-alpha

To compare the expressions of transforming growth factor alpha (TGFalpha), tumor necrosis factor alpha (TNFalpha), and vascular endothelial growth factor (VEGF) between pheochromocytoma (PHEO) tissues and normal adrenal medulla tissues.. The mRNA expressions of TGFalpha, TNFalpha, and VEGF detected by RT-PCR, were compared between 22 PHEO tissues and 18 normal adrenal medulla tissues (according with the principle of medical ethnics). Immunohistochemistry staining was performed on 27 PHEO tissues and 14 normal adrenal medulla tissues. The comparisons of the protein expression of TGFalpha, TNFalpha, and VEGF were analyzed in both of PHEO tissues and normal adrenal medulla tissues.. Compared with normal adrenal medulla tissues, the expressions of TGFalpha and TNFalpha mRNA and protein were higher in PHEO tissues, and VEGF145 mRNA expression was also higher in PHEO tissues, while there was no significant difference of the mRNA expression of VEGF121 and VEGF165 between these two tissues. Positive staining rates for VEGF of endothelial cells and tumor cells were higher in PHEO tissues than in normal adrenal medulla tissues. Expressions of the TGFalpha, TNFalpha, and VEGF protein were higher in extra-adrenal PHEO than in adrenal PHEO. The TNFalpha immunohistochemistry staining rate was higher in the malignant or multiple PHEO than in the benign or single PHEO.. The mRNA and protein expressions of TGFalpha, TNFalpha, and VEGF are higher in PHEO tissues than those in normal adrenal medulla tissues. Expressions of these cytokines vary in PHEO with different characteristic.

Topics: Adrenal Gland Neoplasms; Adrenal Medulla; Humans; Pheochromocytoma; RNA, Messenger; Transforming Growth Factor alpha; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factors

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.

Topics: Adrenal Gland Neoplasms; Aged; Antibodies, Monoclonal; Autoreceptors; Carcinoid Tumor; Carcinoma, Medullary; Cell Division; DNA, Neoplasm; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Proteins; Neuroendocrine Tumors; Paraganglioma; Pheochromocytoma; Retroperitoneal Neoplasms; RNA, Messenger; RNA, Neoplasm; Thyroid Neoplasms; Transforming Growth Factor alpha; Tumor Cells, Cultured