transforming-growth-factor-alpha and Endocrine-Gland-Neoplasms

Endocrine tumors are characteristically hypervascularized. This property recalls that of normal endocrine tissues, which possess a dense and specialized capillary network. The cellular and molecular mechanisms of the angiogenesis process associated with endocrine tumorigenesis are poorly known. Most normal endocrine cells constituvely express high levels of angiogenic factors, such as VEGF, which likely play an important role in the development of the characteristic vascular architecture of normal endocrine tissues. Clinical and experimental data suggest that a surexpression of such angiogenic factors is unlikely to be involved in the induction of the angiogenic process associated with endocrine tumorigenesis. In contrast, according to some experimental observations, the loss of endocrine-specific anti-angiogenic factors may be required for the initiation of the angiogenic process and the transition from endocrine hyperplasia to endocrine neoplasia. Such inhibitory factors remain to be identified and characterized. A better understanding of the mechanisms of angiogenesis in endocrine tumors is important for the delineation of novel therapeutic strategies.

Topics: Animals; Capillaries; Cell Division; Endocrine Gland Neoplasms; Endocrine System; Endothelial Growth Factors; Endothelium, Vascular; Humans; Lymphokines; Mice; Mice, Transgenic; Neovascularization, Pathologic; Pancreatic Neoplasms; Transforming Growth Factor alpha; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Transforming growth factor-alpha (TGF-alpha) is a polypeptide growth factor that binds to the epidermal growth factor receptor and is though to stimulate cell proliferation. It has been believed to play a role in tumor initiation by inducing the reversible transformed phenotype; overexpression of TGF-alpha may be important for tumor progression via autocrine stimulation and oncogene overexpression. Expression of TGF-alpha and the epidermal growth factor receptor has been documented in several nontumorous tissues and in a variety of tumors. This study used immunohistochemistry to localize TGF-alpha expression in normal and neoplastic endocrine tissues. Transforming growth factor-alpha was found in nontumorous hypothalamus, pituitary, thyroid, parathyroid, adrenal cortex and medulla, and pancreatic islets. Immunoreactivity was detected in most benign and malignant tumors of these tissues, as well as in endocrine neoplasms of the lung and gastrointestinal tract. Hypothalamic gangliocytomas, pheochromocytomas, and adrenal cortical carcinomas showed consistently greater immunoreactivity than their normal counterpart, but there was no correlation between degree of reactivity and tumor grade, stage, or hormone content. These results suggest that in endocrine tissues, TGF-alpha is unlikely to prove useful as a tumor marker but that the growth factor may play a role in both normal physiology and tumorigenesis.

Topics: Adrenal Glands; Digestive System; Endocrine Gland Neoplasms; Endocrine Glands; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Hypothalamus; Immunohistochemistry; Lung; Male; Pancreas; Parathyroid Glands; Pituitary Gland; RNA, Messenger; Thyroid Gland; Transforming Growth Factor alpha