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Elucidação do papel de brachyury na diferenciação de distintas linhagens celulares: implicações na tumorigénese
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Abstract(s)
Brachyury é um fator de transcrição expresso muito cedo no desenvolvimento embrionário enquanto marcador dos precursores de mesendoderme. Este apresenta níveis elevados de expressão nos tecidos derivados da mesoderme, que diminuem e desaparecem à medida que as células se diferenciam em estruturas definitivas. De acordo com estes dados, verificou-se que em tumores de tecidos derivados da mesendoderme (como por exemplo, cancro da próstata e gastrointestinal), a presença de Brachyury está associada a um maior grau de indiferenciação celular, resultando em pior prognóstico, pior resposta terapêutica, maior recorrência e menor sobrevida. Inversamente, em tumores de tecidos derivados da neuroectoderme embrionária, tais como os gliomas, Brachyury comporta-se como um gene supressor tumoral, sendo um biomarcador independente de bom prognóstico e favorecendo a resposta terapêutica. O nosso grupo de investigação possui dados preliminares que demostram a expressão de Brachyury associada à diferenciação do sistema nervoso central. Para além desses, outros dados do nosso grupo indicam que a proteína Hairy1, pertencente ao relógio molecular embrionário, não só co-localiza com o marcador mesodermal Brachyury (T) durante a gastrulação, como também interage fisicamente com esta proteína.
Neste trabalho, foi realizada uma caracterização da expressão de Brachyury e de Hairy1 no embrião de galinha em desenvolvimento, no tempo e no espaço por imunohistoquímica. Para além disso, a presença de Brachyury e Hairy1 na diferenciação da mesoderme e da neuroectoderme foi estudada através da deteção de isoformas ou de complexos proteicos diferentes por western blot. Os nossos resultados mostram que Brachyury e Hairy1 estão a ser expressos em tecidos neurais do embrião de galinha.
A elucidação do papel de Brachyury na diferenciação de cada linhagem celular irá contribuir para uma melhor compreensão dos processos tumorigénicos em que está implicado.
Brachyury is a transcription factor expressed very early in embryonic development as a marker of mesendoderm precursors. It shows high levels of expression in tissues derived from the mesoderm, which decrease and disappear as the cells differentiate into definitive structures. According to these data, it was found that in tumor tissues derived from the mesendoderm (such as prostate and gastrointestinal cancer), the presence of Brachyury is associated with a greater degree of cellular undifferentiation, resulting in worse prognosis, worse response treatment, greater recurrence and shorter survival. Conversely, in embryonic neuroectoderm-derived tissue tumors, such as gliomas, Brachyury behaves as a tumor suppressor gene, being an independent biomarker of good prognosis and favoring the therapeutic response. Our research group has preliminary data demonstrating Brachyury expression associated with central nervous system differentiation. In addition to these, other data from our group indicate that the Hairy1 protein, belonging to the embryo molecular clock, not only co-localizes with the mesodermal marker Brachyury (T) during gastrulation, but also interacts physically with this protein. In this work, we performed the characterization of the expression of Brachyury and Hairy1 in the developing chicken embryo by immunohistochemistry. Furthermore, the presence of Brachyury and Hairy1 in the differentiation of mesoderm and neuroectoderm was studied through the detection of different protein isoforms or complexes by western blot. Our results show that Brachyury and Hairy1 are being expressed in chicken embryo neural tissues.
Brachyury is a transcription factor expressed very early in embryonic development as a marker of mesendoderm precursors. It shows high levels of expression in tissues derived from the mesoderm, which decrease and disappear as the cells differentiate into definitive structures. According to these data, it was found that in tumor tissues derived from the mesendoderm (such as prostate and gastrointestinal cancer), the presence of Brachyury is associated with a greater degree of cellular undifferentiation, resulting in worse prognosis, worse response treatment, greater recurrence and shorter survival. Conversely, in embryonic neuroectoderm-derived tissue tumors, such as gliomas, Brachyury behaves as a tumor suppressor gene, being an independent biomarker of good prognosis and favoring the therapeutic response. Our research group has preliminary data demonstrating Brachyury expression associated with central nervous system differentiation. In addition to these, other data from our group indicate that the Hairy1 protein, belonging to the embryo molecular clock, not only co-localizes with the mesodermal marker Brachyury (T) during gastrulation, but also interacts physically with this protein. In this work, we performed the characterization of the expression of Brachyury and Hairy1 in the developing chicken embryo by immunohistochemistry. Furthermore, the presence of Brachyury and Hairy1 in the differentiation of mesoderm and neuroectoderm was studied through the detection of different protein isoforms or complexes by western blot. Our results show that Brachyury and Hairy1 are being expressed in chicken embryo neural tissues.
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Keywords
Brachyury Diferenciação Sistema nervoso central Hairy1 Iumorigénese