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https://ir.cnu.edu.tw/handle/310902800/32673
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| 標題: | Activation of Aryl Hydrocarbon Receptor by Kynurenine Impairs Progression and Metastasis of Neuroblastoma |
| 作者: | Wu, Pei-Yi
Yu, I-Shing
Lin, Yueh-Chien
Chang, Yu-Tzu
Chien-Chin Chen(陳建欽)
Lin, Kuan-Hung
Tseng, Tzu-Hsuan
Kargren, Mati
Tai, Yu-Ling
Shen, Tang-Long
Liu, Yen-Lin
Wang, Bo-Jeng
Chang, Chi-Hao
Chen, Wei-Min
Juan, Hsueh-Fen
Huang, Shiu-Feng
Chan, Ya-Yun
Liao, Yung-Feng
Hsu, Wen-Ming
Lee, Hsinyu |
| 貢獻者: | Acad Sinica, Inst Cellular & Organism Biol
Natl Taiwan Univ, Coll Med, Lab Anim Ctr
Natl Taiwan Univ, Dept Life Sci
Chia Yi Christian Hosp, Dept Pathol
Chia Nan Univ Pharm & Sci, Dept Cosmet Sci
Natl Taiwan Univ, Dept Plant Pathol & Microbiol
Natl Taiwan Univ, Ctr Biotechnol
Taipei Med Univ Hosp, Dept Pediat
Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan
Natl Taiwan Univ Hosp, Dept Surg, Taipei, Taiwan
Natl Taiwan Univ, Coll Med |
| 關鍵字: | BREAST-CANCER CELLS
AH RECEPTOR
KISS-1 EXPRESSION
GENE-EXPRESSION
N-MYC
PROTEIN
PROLIFERATION
IDENTIFICATION
INDUCTION
MELANOMA |
| 日期: | 2019-11 |
| 上傳時間: | 2020-07-29 13:54:43 (UTC+8) |
| 出版者: | AMER ASSOC CANCER RESEARCH |
| 摘要: | Neuroblastoma is the most common malignant disease of infancy, and amplification of the MYCN oncogene is closely associated with poor prognosis. Recently, expression of MYCN was shown to be inversely correlated with aryl hydrocarbon receptor (AHR) expression in neuroblastoma, and overexpression of AHR downregulated MYCN expression, promoting cell differentiation. Therefore, we further investigated the potential of AHR to serve as a prognostic indicator or a therapeutic target in neuroblastoma. First, the clinical significance of AHR in neuroblastoma was examined. Positive AHR immunostaining strongly correlated with differentiated histology of neuroblastoma and predicted better survival for patients. The mouse xenograft model showed that overexpression of AHR significantly suppressed neuroblastoma tumor growth. In addition, activation of AHR by the endogenous ligand kynurenine inhibited cell proliferation and promoted cell differentiation in vitro and in vivo. kynurenine treatment also upregulated the expression of KISS1, a tumor metastasis suppressor, and attenuated metastasis in the xenograft model. Finally, analysis of KISS1 levels in neuroblastoma patient tumors using the R2: Genomics Analysis and Visualization Platform revealed that KISS1 expression positively correlated with AHR, and high KISS1 expression predicted better survival for patients. In conclusion, our results indicate that AHR is a novel prognostic biomarker for neuroblastoma, and that overexpression or activation of AHR offers a new therapeutic possibility for patients with neuroblastoma. Significance: These findings show that AHR may function as a tumor suppressor in childhood neuroblastoma, potentially influencing the aetiologic and therapeutic targeting of the disease. |
| 關聯: | Cancer Research, v.79, n.21, pp.5550-5562 |
| 顯示於類別: | [化妝品應用與管理系(所)] 期刊論文
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