Tissue-specific transcription factors in progression of epithelial tumors.
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Dedifferentiation and epithelial-mesenchymal transition are important steps in epithelial tumor progression. A central role in the control of functional and morphological properties of different cell types is attributed to tissue-specific transcription factors which form regulatory cascades that define specification and differentiation of epithelial cells during embryonic development. The main principles of the action of such regulatory systems are reviewed on an example of a network of hepatocyte nuclear factors (HNFs) which play a key role in establishment and maintenance of hepatocytes--the major functional type of liver cells. HNFs, described as proteins binding to promoters of most hepatospecific genes, not only control expression of functional liver genes, but are also involved in regulation of proliferation, morphogenesis, and detoxification processes. One of the central components of the hepatospecific regulatory network is nuclear receptor HNF4alpha. Derangement of the expression of this gene is associated with progression of rodent and human hepatocellular carcinomas (HCCs) and contributes to increase of proliferation, loss of epithelial morphology, and dedifferentiation. Dysfunction of HNF4alpha during HCC progression can be either caused by structural changes of this gene or occurs due to modification of up-stream regulatory signaling pathways. Investigations preformed on a model system of the mouse one-step HCC progression have shown that the restoration of HNF4alpha function in dedifferentiated cells causes partial reversion of malignant phenotype both in vitro and in vivo. Derangement of HNFs function was also described in other tumors of epithelial origin. We suppose that tissue-specific factors that underlie the key steps in differentiation programs of certain tissues and are able to receive or modulate signals from the cell environment might be considered as promising candidates for the role of tumor suppressors in the tissue types where they normally play the most significant role. (+info)
Role of Sox-9, ER81 and VE-cadherin in retinoic acid-mediated trans-differentiation of breast cancer cells.
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Myogenic transdifferentiation of menstrual blood-derived cells.
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Cells with myogenic potential are present in many tissues, and these cells readily form skeletal muscle in culture. We here focus on menstrual blood as another cell source for regenerative medicine. Menstrual blood-derived cells have high replicative ability, similar to progenitors or stem cells, and transdifferentiate or meta-differentiate into myocytes in vitro at unexpectedly high frequencies. This unique phenotype can be explained by histological and embryological aspects of the endometrium. The remarkable myogenic capability of these cells enables us to "rescue" dystrophied myocytes of the mdx model of Duchenne muscular dystrophy through cell fusion and transdifferentiation. Endometrial cells supplied as a form of menstrual blood-tissue mixture can be used for cell-based therapy in addition to a place for embryo implantation. (+info)
GDF15 triggers homeostatic proliferation of acid-secreting collecting duct cells.
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