Ancrile Brooke, Lim Kian-Huat, Counter Christopher M
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Genes Dev. 2007 Jul 15;21(14):1714-9. doi: 10.1101/gad.1549407.
Ras is mutated to remain in the active oncogenic state in many cancers. As Ras has proven difficult to target therapeutically, we searched for secreted, druggable proteins induced by Ras that are required for tumorigenesis. We found that Ras induces the secretion of cytokine IL6 in different cell types, and that knockdown of IL6, genetic ablation of the IL6 gene, or treatment with a neutralizing IL6 antibody retard Ras-driven tumorigenesis. IL6 appears to act in a paracrine fashion to promote angiogenesis and tumor growth. Inhibiting IL6 may therefore have therapeutic utility for treatment of cancers characterized by oncogenic Ras mutations.
在许多癌症中，Ras发生突变并维持在致癌活性状态。由于已证明Ras难以成为治疗靶点，我们寻找由Ras诱导分泌的、可成药的、肿瘤发生所必需的蛋白质。我们发现，Ras在不同细胞类型中诱导细胞因子IL6的分泌，并且敲低IL6、对IL6基因进行基因敲除或用中和性IL6抗体处理可延缓Ras驱动的肿瘤发生。IL6似乎以旁分泌方式发挥作用，促进血管生成和肿瘤生长。因此，抑制IL6可能对治疗以致癌Ras突变为特征的癌症具有治疗作用。
