Cisplatin sensitivity mediated by NKX2-1 in lung adenocarcinoma is dependent on p53 mutational status via modulating TNFSF10 expression

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Title:	Cisplatin sensitivity mediated by NKX2-1 in lung adenocarcinoma is dependent on p53 mutational status via modulating TNFSF10 expression
Authors:	Chen, Ming-Jenn Chen, Po-Ming Wang, Lee Shen, Ching-Ju Chen, Chi-Yi Lee, Huei
Contributors:	Chi Mei Med Ctr, Dept Surg Chia Nan Univ Pharm & Sci, Coll Leisure & Recreat Management, Dept Sports Management Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery Chung Shan Med Univ, Dept Publ Hlth Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Gynecol & Obstet, Coll Med Chung Shan Med Univ Hosp, Dept Surg
Keywords:	NKX2-1 TNFSF10 cisplatin p53 mutational status lung adenocarcinoma
Date:	2020
Issue Date:	2022-11-18 11:24:08 (UTC+8)
Publisher:	E-Century Publishing Corp
Abstract:	NKX2-1 was shown to enhance cisplatin sensitivity in KRAS-mutated cells, but it conferred cisplatin resistance in EGFR-mutated lung adenocarcinoma cells. However, NKX2-1 as a dual role in tumor progression depended on p53 mutational status via modulation of the NF-kappa B pathway. We hypothesized that NKX2-1 may confer cisplatin resistance in p53-mutated (p53-MT) lung adenocarcinoma cells but may enhance cisplatin sensitivity in wild-type (p53-WT) cells. In the present study, six p53-MT and -p53-WT cell lines were treated with various concentrations of cisplatin to calculate the inhibitory concentration of cisplatin for 50% cell viability (IC50). The IC50 value was positively correlated with NKX2-1 expression in the p53-MT cells but negatively correlated in the p53-WT cells. TNFSF10 was identified in a microarray analysis as a potential candidate responsible for NKX2-1-mediated apoptosis induced by cisplatin. The retrospective study evaluated 97 surgically resected lung adenocarcinoma patients receiving cisplatinbased chemotherapy to explore the possible association between NKX2-1 expression and tumor response. Patients with higher TNFSF10 mRNA levels, as determined by real-time reverse transcription-polymerase Chain Reaction (RT-PCR), typically showed an favorable response when compared with patients with lower TNFSF10 mRNA levels. Additionally, the association of higher TNFSF10 mRNA levels with favorable response was only revealed in p53-WT patients, not in p53-MT patients. Higher NKX2-1 mRNA levels were associated with an unfavorable response in patients with p53-MT tumors but a favorable response in patients with p53-WT tumors. In summary, modulation of TNFSF10 expression by NKX2-1 may be a potential indicator for predicting the response to cisplatin-based chemotherapy in patients with lung adenocarcinomas.
Relation:	American Journal of Cancer Research, v.10, n.4, pp.9
Appears in Collections:	[Dept. of Sports Management] Periodical Articles

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