999 resultados para A7
Resumo:
Medulloblastoma (MB) is the most common malignant brain tumor in children and is associated with a poor outcome. cMYC amplification characterizes a subgroup of MB with very poor prognosis. However, there exist so far no targeted therapies for the subgroup of MB with cMYC amplification. Here we used kinome-wide RNA interference screening to identify novel kinases that may be targeted to inhibit the proliferation of c-Myc-overexpressing MB. The RNAi screen identified a set of 5 genes that could be targeted to selectively impair the proliferation of c-Myc-overexpressing MB cell lines: AKAP12 (A-kinase anchor protein), CSNK1α1 (casein kinase 1, alpha 1), EPHA7 (EPH receptor A7) and PCTK1 (PCTAIRE protein kinase 1). When using RNAi and a pharmacological inhibitor selective for PCTK1, we could show that this kinase plays a crucial role in the proliferation of MB cell lines and the activation of the mammalian target of rapamycin (mTOR) pathway. In addition, pharmacological PCTK1 inhibition reduced the expression levels of c-Myc. Finally, targeting PCTK1 selectively impaired the tumor growth of c-Myc-overexpressing MB cells in vivo. Together our data uncover a novel and crucial role for PCTK1 in the proliferation and survival of MB characterized by cMYC amplification.
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1906/01/11 (A7,N1).
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1906/12/13 (A7,N49).
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1906/12/20 (A7,N50).
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1906/12/06 (A7,N48).
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1906/11/29 (A7,N47).
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1906/11/22 (A7,N46).
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1906/11/08 (A7,N44).
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1906/11/15 (A7,N45).
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1906/10/25 (A7,N42).
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1906/11/01 (A7,N43).
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1906/10/11 (A7,N40).
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1882 (N8,A7)-1883.
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1848 (A7,T7,SER2).
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1875/03/28 (A7,T1,N232).
