Artemin is oncogenic for human mammary carcinoma cells
Artemin is oncogenic for human mammary carcinoma cells
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Artemin 对人乳腺癌细胞具有致癌作用
DOI：
10.1038/onc.2009.66
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发表时间：
2009-05-14
期刊：
影响因子：
8
通讯作者：
Lobie, P. E.
中科院分区：
文献类型：
--
作者：
Kang, J.;Perry, J. K.;Lobie, P. E.
我们报道，青蒿素是胶质细胞系源性神经营养因子配体家族的成员，是人类乳腺癌的致癌因子。青蒿素在许多人乳腺癌细胞系中都有表达。在乳腺癌细胞中强制表达青蒿素可增加非贴壁生长，增加软琼脂和三维Matrigel中的集落形成，并促进分散的细胞表型，增强迁移和侵袭。此外，在异种移植模型中，强制表达青蒿素会增加肿瘤的大小，并导致高增殖、低分化和侵袭性肿瘤。Oncomine中的表达数据表明，青蒿素的高表达与化疗后的残留疾病、转移、复发和死亡显著相关。在65%的乳腺癌中可以检测到青蒿素蛋白，它的表达与患者队列中总体生存率的降低有关。用小干扰RNA耗尽内源性青蒿素，或抗体抑制青蒿素，可降低乳腺癌细胞的致瘤性和侵袭性。因此，青蒿素是人类乳腺癌的致癌因素，而抑制乳腺癌中青蒿素功能的靶向治疗方法值得考虑。
We report that artemin, a member of the glial cell line-derived neurotrophic factor family of ligands, is oncogenic for human mammary carcinoma. Artemin is expressed in numerous human mammary carcinoma cell lines. Forced expression of artemin in mammary carcinoma cells results in increased anchorage-independent growth, increased colony formation in soft agar and in three-dimensional Matrigel, and also promotes a scattered cell phenotype with enhanced migration and invasion. Moreover, forced expression of artemin increases tumor size in xenograft models and leads to highly proliferative, poorly differentiated and invasive tumors. Expression data in Oncomine indicate that high artemin expression is significantly associated with residual disease after chemotherapy, metastasis, relapse and death. Artemin protein is detectable in 65% of mammary carcinoma and its expression correlates to decreased overall survival in the cohort of patients. Depletion of endogenous artemin with small interfering RNA, or antibody inhibition of artemin, decreases the oncogenicity and invasiveness of mammary carcinoma cells. Artemin is therefore oncogenic for human mammary carcinoma, and targeted therapeutic approaches to inhibit artemin function in mammary carcinoma warrant consideration.