Navegando por Palavras-chave "Fator de transcrição E2F1"

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    Expressão do gene E2F1 em células progenitoras do cerebelo durante o desenvolvimento pós-natal
    (Universidade Federal de São Paulo (UNIFESP), 2009-07-29) Suzuki, Daniela Emi [UNIFESP]; Okamoto, Oswaldo Keith [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Throughout the cerebellum development, several molecular mechanisms are crucial in the processes of proliferation and differentiation of stem cells and progenitor cells of the cerebellum. The lack of mechanisms for proliferation and differentiation of stem cells and neural progenitors may contribute to the emergence of genetic changes, resulting in neoplastic transformation. Mutations or aberrant expression of genes related to molecular pathways can be found in human cancers. Although the involvement of NOTCH, SHH and WNT pathways in neurogenesis and in the development of tumors is known, the fine mechanisms of regulation involved in these processes remain unclear. Accordingly, this study aimed to analyze the profile of expression of the E2F1 gene, gene encoding of transcription factor involved in the SHH and WNT signaling pathways in ordinary cerebellar neuroprogenitors cells throughout the cerebellar postnatal development, in order to understand its relevance in the physiological context and possible involvement in neoplastic transformation. The results confirmed the progression of maturation in rat cerebellum during the postnatal period up to age P12. During this period, the results showed that progenitor cells differentiate into cerebellar granular neurons, as decreased cellular proliferative capacity. During this period of maturation, granular progenitor cells showed higher proliferation index in P3, so period that from P3 the rate declined reaching baseline levels at P12, age of a mature cerebellum, evidenced by the presence of ten sheets and cerebellar layers distinct granular. Besides evidence citoarquitetonics observed by histologic evaluation using cresyl-violet staining and by immunofluorescence, the processes of cellular proliferation, differentiation and apoptosis were based by the pattern of expression of specific genes found in cerebellar granular progenitor cells. The analysis of the expression profile of transcription factor E2F1 showed that this expression is present throughout the developing postnatal cerebellum, and significantly higher expression in age P12, when the rates of cell proliferation returned to baseline levels, with level of expression of p18Ink4 significantly increased. Another relevant correlation was detected between gene expression of E2F1 and WNT4, so the results showed a higher expression of WNT4 in P9, the period preceding the peak of expression of E2F1 in P12. This interaction is consistent with the possible regulation by WNT-E2F1 feedback. Thus, together, these results indicate that expression of E2F1 is associated with an inhibition of proliferation of granular progenitor cells at the end of the maturation of the cerebellum of rats.
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    O uso de interferência por RNA para a análise da função do gene E2F1 na progressão do ciclo celular em células tumorais
    (Universidade Federal de São Paulo (UNIFESP), 2010-10-27) Oliveira, Maria Theresa de [UNIFESP]; Monteiro, Hugo Pequeno [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    E2F1 belongs to a family of transcription factors and plays a central role in controlling the expression of genes related to regulation of the cell-cycle progression, since it activates genes involved in DNA synthesis. The activity of E2F1 is regulated by pRB protein, that when phosphorylated by cyclin-dependent kinases cyclins (Cyclins/CDK) releases this transcription factor, thereby promoting proliferation. The dysfunction of the complex regulatory pathway of cell division can lead to excessive proliferation, which overexpression of E2F1 is quite common in different types of tumors. This phenomenon may be the main factor for the high proliferation of tumor cells. Thus, inhibition of E2F1 activity by RNA interference (RNAi) may be promising as a treatment for decreased proliferation of melanoma cells. Therefore, the purpose of this work is the inactivation of the E2f1 gene through RNAi in B16mCAR cells, derived from C57BL/6’s melanoma and overexpresses the CAR receptor, and also verifies the effects of its absence on cell proliferation in vitro and in vivo.