scholarly journals Introduction of exogenous wild‑type p53 mediates the regulation of oncoprotein�18/stathmin signaling via nuclear factor‑κB in non‑small cell lung cancer NCI‑H1299 cells

2019 ◽  
Author(s):  
Sangyan Chen ◽  
Yan Zhao ◽  
Fang Shen ◽  
Dan Long ◽  
Ting Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Nuclear Factor Κb ◽  
Small Cell ◽  
Nuclear Factor ◽  
Wild Type ◽  
Small Cell Lung ◽  
Oncoprotein 18 ◽  
Wild Type P53

scholarly journals Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation

2020 ◽  
Vol 21 (9) ◽  
pp. 3392
Author(s):  
Peizhong Kong ◽  
K.N. Yu ◽  
Miaomiao Yang ◽  
Waleed Abdelbagi Almahi ◽  
Lili Nie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Wild Type ◽  
Small Cell Lung ◽  
H460 Cells ◽  
Wild Type P53

Micheliolide (MCL) has shown promising anti-inflammatory and anti-tumor efficacy. However, whether and how MCL enhances the sensitivity of non-small-cell lung cancer (NSCLC) to radiotherapy are still unknown. In the present paper, we found that MCL exerted a tumor cell killing effect on NSCLC cells in a dose-dependent manner, and MCL strongly sensitized p53-deficient NSCLC cells, but not the cells with wild-type p53 to irradiation (IR). Meanwhile, MCL markedly inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) after IR and hypoxic exposure in H1299 and Calu-1 cells rather than in H460 cells. Consistently, radiation- or hypoxia-induced expression of vascular endothelial growth factor (VEGF) was also significantly inhibited by MCL in H1299 and Calu-1 cells, but not in H460 cells. Therefore, inhibition of the HIF-1α pathway might, at least in part, contribute to the radiosensitizing effect of MCL. Further study showed that MCL could accelerate the degradation of HIF-1α through the ubiquitin-proteosome system. In addition, the transfection of wild-type p53 into p53-null cells (H1299) attenuated the effect of MCL on inhibiting HIF-1α expression. These results suggest MCL effectively sensitizes p53-deficient NSCLC cells to IR in a manner of inhibiting the HIF-1α pathway via promoting HIF-1α degradation, and p53 played a negative role in MCL-induced HIF-1α degradation.

Wild-Type p53 Overexpression and Its Correlation With MDM2 and p14ARF Alterations: An Alternative Pathway to Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (1) ◽  
pp. 154-164 ◽  
Author(s):  
Yu-Chien Wang ◽  
Ruo-Kai Lin ◽  
Yi-Hung Tan ◽  
Jung-Ta Chen ◽  
Chih-Yi Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
P53 Protein ◽  
Small Cell ◽  
Sequencing Analysis ◽  
Nuclear Staining ◽  
Wild Type ◽  
Small Cell Lung ◽  
Wild Type P53

Purpose We found a relatively reduced frequency of p53 mutation with a much greater frequency of p53 protein overexpression, which reflected stabilization of p53 protein in the absence of p53 gene mutation. Therefore, we investigated the possibility of alternative mechanisms leading to p53 protein stabilization. Patients and Methods We performed gene and protein alteration studies on p53 and its upstream effectors, MDM2 and p14ARF, in tumors from 94 non–small-cell lung cancer (NSCLC) patients. Results Immunohistochemical and sequencing analyses indicated that 37 tumors showed overexpression of wild-type p53. An absence of nuclear staining of MDM2 protein was found in 95% of these tumors (35 of 37; P < .001). The tumors with negative MDM2 staining showed a significantly high concordance of loss of Akt activity and low MDM2 mRNA expression (P < .001). Sequencing analysis revealed five distinct MDM2 splicing variants disrupting the conserved p53 binding domain. Corresponding variant proteins were detected in three lung cancer cell lines using the Western blot analysis. Our results also indicated that among the tumors with overexpression of the wild-type p53, 92% (34 of 37) showed immunoreactivity to p14ARF (P = .001). In addition, the deregulation of p53 and MDM2 genes was significantly associated with squamous lung cancer (P < .05) and was correlated with advanced stages (P < .05) and poor prognosis (P < .05). Conclusion Our data suggest that immunopositivity of p14ARF together with a low expression of MDM2 contributes to accumulation of the wild-type p53, and that deregulation of the p53-MDM2-p14ARF pathway is important in the pathogenesis and outcome of a subset of NSCLC.

The cardenolide UNBS1450 is able to deactivate nuclear factor κB–mediated cytoprotective effects in human non–small cell lung cancer cells

2006 ◽  
Vol 5 (2) ◽  
pp. 391-399 ◽  
Author(s):  
Tatjana Mijatovic ◽  
Anne Op De Beeck ◽  
Eric Van Quaquebeke ◽  
Janique Dewelle ◽  
Francis Darro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Nuclear Factor Κb ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Nuclear Factor ◽  
Small Cell Lung
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