Artemin-stimulated progression of human non-small cell lung carcinoma is mediated by BCL2
| Autor: | Peter E. Lobie, Xiangjun Kong, Michael Steiner, Jian Kang, Graeme C. Fielder, Zhengsheng Wu, Dong-Xu Liu, Jian-Zhong Tang, Jo K. Perry, Zhinan Yin, Tao Zhu |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Lung Neoplasms Cell Survival Cell Artemin Nerve Tissue Proteins Biology Metastasis Mice Downregulation and upregulation Neurotrophic factors Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Cell Adhesion Animals Humans Neoplasm Invasiveness neoplasms Cell Proliferation Matrigel Cell growth medicine.disease Xenograft Model Antitumor Assays respiratory tract diseases Neoplasm Proteins Gene Expression Regulation Neoplastic Drug Combinations medicine.anatomical_structure Oncology Proto-Oncogene Proteins c-bcl-2 Immunology Cancer research Disease Progression Proteoglycans Collagen Laminin Signal transduction |
| Zdroj: | Molecular cancer therapeutics. 9(6) |
| ISSN: | 1538-8514 |
| Popis: | 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. ©2010 AACR. |
| Databáze: | OpenAIRE |
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