The Liggins Institute, University of Auckland, 2-6 Park Avenue, Private Bag 92019 Auckland, New Zealand.
Endocrinology. 2010 Mar;151(3):909-20. doi: 10.1210/en.2009-0979. Epub 2010 Jan 29.
Here, we provide evidence for a functional role of artemin (ARTN) in progression of endometrial carcinoma (EC). Increased ARTN protein expression was observed in EC compared with normal endometrial tissue, and ARTN protein expression in EC was significantly associated with higher tumor grade and invasiveness. Forced expression of ARTN in EC cells significantly increased total cell number as a result of enhanced cell cycle progression and cell survival. In addition, forced expression of ARTN significantly enhanced anchorage-independent growth and invasiveness of EC cells. Moreover, forced expression of ARTN increased tumor size in xenograft models and produced highly proliferative, poorly differentiated, and invasive tumors. The ARTN-stimulated increases in oncogenicity and invasion were mediated by increased expression and activity of AKT1. Small interfering RNA-mediated depletion or antibody inhibition of ARTN significantly reduced oncogenicity and invasion of EC cells. Thus, inhibition of ARTN may be considered as a potential therapeutic strategy to retard progression of EC.
在这里，我们提供了 artemin（ARTN）在子宫内膜癌（EC）进展中具有功能作用的证据。与正常子宫内膜组织相比，EC 中观察到 ARTN 蛋白表达增加，并且 ARTN 蛋白在 EC 中的表达与更高的肿瘤分级和侵袭性显著相关。在 EC 细胞中强制表达 ARTN 会导致细胞周期进程和细胞存活增强，从而显著增加总细胞数。此外，强制表达 ARTN 会显著增强 EC 细胞的无锚定生长和侵袭能力。此外，强制表达 ARTN 会增加异种移植模型中的肿瘤大小，并产生高增殖、低分化和侵袭性肿瘤。ARTN 刺激的致癌性和侵袭性增加是通过 AKT1 的表达和活性增加介导的。小干扰 RNA 介导的 ARTN 耗竭或抗体抑制显著降低了 EC 细胞的致癌性和侵袭性。因此，抑制 ARTN 可能被认为是一种潜在的治疗策略，可延缓 EC 的进展。
