Cytokine overexpression and constitutive NFkappaB in cancer.
Cytokine overexpression and constitutive NFkappaB in cancer.
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作者：
T. Lu;G. Stark
NFkappaB家族转录因子，免疫反应的中枢介质，也参与肿瘤的发生。正常潜伏的NFkappaB的调控缺失对许多癌症中观察到的生长失控、细胞凋亡抵抗和转移倾向起着重要作用。因此，激活NFkappaB的途径是可能有助于预防或治疗癌症的新药物的有希望的靶点。我们发现，通过结合细胞表面受体激活NFkappaB的多种细胞因子的异常分泌是癌症中构成性NFkappaB活性的主要原因之一。一项新的发现是，由这些细胞中的一些分泌的tgf - β的潜伏形式可以激活NFkappaB。为了了解这种异常细胞因子分泌的基础，我们正在使用正向遗传方法来识别癌细胞中的特定致病突变。
The NFkappaB family of transcription factors, central mediators of immune responses, are also involved in oncogenesis. Loss of regulation of the normally latent NFkappaB contributes importantly to the deregulated growth, resistance to apoptosis and propensity to metastasize observed in many cancers. Thus, pathways for activation of NFkappaB are promising targets for new agents that may help to prevent or treat cancer. We find that the abnormal secretion of multiple cytokines that activate NFkappaB by binding to cell-surface receptors is one of the major causes of constitutive NFkappaB activity in cancer. A novel finding is that the latent form of TGFbeta, secreted by some of these cells, can activate NFkappaB. To understand the basis of this abnormal cytokine secretion, we are using forward genetic methods to identify specific causative mutations in cancer cells.