Artemin-Stimulated Progression of Human Non-Small Cell Lung Carcinoma Is Mediated by BCL2

作者：Tang Jian Zhong; Kong Xiang Jun; Kang Jian; Fielder Graeme C; Steiner Michael; Perry Jo K; Wu Zheng Sheng; Yin Zhinan; Zhu Tao; Liu Dong Xu; Lobie Peter E^*

来源：Molecular Cancer Therapeutics, 2010, 9(6): 1697-1708.

DOI：10.1158/1535-7163.MCT-09-1077

We herein show that Artemin (ARTN), one of the glial cell line-derived neurotrophic factor family of ligands, promotes progression of human non-small cell lung carcinoma (NSCLC). Oncomine data indicate that expression of components of the ARTN signaling pathway (ARTN, GFRA3, and RET) is increased in neoplastic compared with normal lung tissues; increased expression of ARTN in NSCLC also predicted metastasis to lymph nodes and a higher grade in certain NSCLC subtypes. Forced expression of ARTN stimulated survival, anchorage-independent, and three-dimensional Matrigel growth of NSCLC cell lines. ARTN increased BCL2 expression by transcriptional upregulation, and inhibition of BCL2 abrogated the oncogenic properties of ARTN in NSCLC cells. Forced expression of ARTN also enhanced migration and invasion of NSCLC cells. Forced expression of ARTN in H1299 cells additionally resulted in larger xenograft tumors, which were highly proliferative, invasive, and metastatic. Concordantly, either small interfering RNA-mediated depletion or functional inhibition of endogenous ARTN with antibodies reduced oncogenicity and invasiveness of NSCLC cells. ARTN therefore mediates progression of NSCLC and may be a potential therapeutic target for NSCLC. Mol Cancer Ther; 9(6); 1697-708.

• 出版日期2010-6
• 单位中国科学技术大学; 安徽医科大学; 南开大学