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

GATA transcription factors are structurally-related zinc finger proteins that recognize the consensus DNA sequence WGATAA (the GATA motif), an essential cis-acting element in the promoters and enhancers of many genes. These transcription factors regulate cell fate specification and differentiation in a wide array of tissues. As demonstrated by genetic analyses of mice and humans, GATA factors play pivotal roles in the development, homeostasis, and function of several endocrine organs including the adrenal cortex, ovary, pancreas, parathyroid, pituitary, and testis. Additionally, GATA factors have been shown to be mutated, overexpressed, or underexpressed in a variety of endocrine tumors (e.g., adrenocortical neoplasms, parathyroid tumors, pituitary adenomas, and sex cord stromal tumors). Emerging evidence suggests that GATA factors play a direct role in the initiation, proliferation, or propagation of certain endocrine tumors via modulation of key developmental signaling pathways implicated in oncogenesis, such as the WNT/β-catenin and TGFβ pathways. Altered expression or function of GATA factors can also affect the metabolism, ploidy, and invasiveness of tumor cells. This article provides an overview of the role of GATA factors in endocrine neoplasms. Relevant animal models are highlighted.

Topics: Animals; Biomarkers, Tumor; Endocrine Gland Neoplasms; GATA Transcription Factors; Humans; Mice; Mutation; Neoplasm Invasiveness; Neoplasms, Experimental; Ploidies; Transforming Growth Factor beta; Wnt Signaling Pathway

Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary glands. This review will address the role of TGF-beta in regulating hormone-dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition, will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

Topics: Animals; Cell Transformation, Neoplastic; Drug Design; Endocrine Gland Neoplasms; Homeostasis; Hormones; Humans; Mice; Transforming Growth Factor beta

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