Cigarette smoke induces the expression of Notch3, not Notch1, protein in lung adenocarcinoma

Cheng,Zhenshun; Tan,Qiuyue; Tan,Weijun; Zhang,Li

doi:10.3892/ol.2015.3329

Cigarette smoke induces the expression of Notch3, not Notch1, protein in lung adenocarcinoma

Authors:
- Zhenshun Cheng
- Qiuyue Tan
- Weijun Tan
- Li Zhang
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Affiliations: Department of Respiratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430070, P.R. China
Published online on: June 5, 2015 https://doi.org/10.3892/ol.2015.3329
Pages: 641-646
Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to determine the effect of cigarette smoke on the expression of Notch proteins in lung adenocarcinoma (LAC). Protein expression levels of Notch1 and Notch3 were analyzed using immunohistochemistry in 102 human LAC specimens. Of these, 52 were obtained from smokers and 50 from non‑smokers. In addition, cigarette smoke extract (CSE) at varying concentrations (1, 2.5 and 5%) was administered to A549 cells. The expression of Notch1 and Notch3 protein was then detected by western blot analysis at different time points (0, 8, 24 and 48 h). Of the 102 LAC specimens, 42 (41.2%) were positive for Notch1 and 63 (61.8%) were positive for Notch3. There was no significant difference in the level of Notch1 expression between smokers and non‑smokers with LAC (P>0.05). The positive rate and staining intensity of Notch3 expression were increased in the smokers compared with the non‑smokers (P<0.05). The expression of Notch3 protein in A549 cells increased in a time‑ and dose‑dependent manner following treatment with CSE, whilst the expression of Notch1 protein appeared stable. The results suggested that cigarette smoke was able to induce the expression of Notch3, not Notch1, protein in LAC. The data revealed an upregulation of Notch3 in LAC following cigarette smoke exposure. Such findings may provide a novel therapeutic target for the treatment of LAC.

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1	Stanley KE: Lung cancer and tobacco - a global problem. Cancer Detect Prev. 9:83–89. 1986.PubMed/NCBI
2	Kadara H, Kabbout M and Wistuba II: Pulmonary adenocarcinoma: a renewed entity in 2011. Respirology. 17:50–65. 2012. View Article : Google Scholar : PubMed/NCBI
3	Harris CC: The epidemiology of different histologic types of bronchogenic carcinoma. Cancer Chemother Rep. 4:59–61. 1973.
4	Allen SS: Cigarette smoking among women: how can we help? Minn Med. 97:41–3. 2014.PubMed/NCBI
5	Stellman SD, Muscat JE, Hoffmann D and Wynder EL: Impact of filter cigarette smoking on lung cancer histology. Prev Med. 26:451–456. 1997. View Article : Google Scholar : PubMed/NCBI
6	Hecht SS: Lung carcinogenesis by tobacco smoke. Int J Cancer. 131:2724–2732. 2012. View Article : Google Scholar : PubMed/NCBI
7	Wen J, Fu JH, Zhang W and Guo M: Lung carcinoma signaling pathways activated by smoking. Chin J Cancer. 30:551–558. 2011. View Article : Google Scholar : PubMed/NCBI
8	Galluzzo P and Bocchetta M: Notch signaling in lung cancer. Expert Rev Anticancer Ther. 11:533–540. 2011. View Article : Google Scholar : PubMed/NCBI
9	Donnem T, Andersen S, Al-Shibli K, Al-Saad S, Busund LT and Bremnes RM: Prognostic impact of Notch ligands and receptors in nonsmall cell lung cancer: Coexpression of Notch-1 and vascular endothelial growth factor-A predicts poor survival. Cancer. 116:5676–5685. 2010. View Article : Google Scholar : PubMed/NCBI
10	Jiang X, Zhou JH, Deng ZH, Qu XH, Jiang HY and Liu Y: Expression and significance of Notch1, Jagged1 and VEGF in human non-small cell lung cancer. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 32:1031–1036. 2007.(In Chinese). PubMed/NCBI
11	Huang J, Song H, Liu B, et al: Expression of Notch-1 and its clinical significance in different histological subtypes of human lung adenocarcinoma. J Exp Clin Cancer Res. 32:842013. View Article : Google Scholar : PubMed/NCBI
12	Haruki N, Kawaguchi KS, Eichenberger S, et al: Dominant-negative Notch3 receptor inhibits mitogen-activated protein kinase pathway and the growth of human lung cancers. Cancer Res. 65:3555–3561. 2005. View Article : Google Scholar : PubMed/NCBI
13	Zhou M, Jin WY, Fan ZW and Han RC: Analysis of the expression of the Notch3 receptor protein in adult lung cancer. Oncol Lett. 5:499–504. 2013.PubMed/NCBI
14	Ye YZ, Zhang ZH, Fan XY, et al: Notch3 overexpression associates with poor prognosis in human non-small-cell lung cancer. Med Oncol. 30:5952013. View Article : Google Scholar : PubMed/NCBI
15	Shepherd FA, Crowley J, Van Houtte P, et al International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions: The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol. 2:1067–1077. 2007. View Article : Google Scholar : PubMed/NCBI
16	Travis WD, Garg K, Franklin WA, et al: Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical importance and research relevance of the 2004 World Health Organization pathologic criteria. J Thorac Oncol. 1:S13–S19. 2006. View Article : Google Scholar : PubMed/NCBI
17	Zhang L, Cheng Z, Liu W and Wu K: Expression of interleukin (IL)-10, IL-17A and IL-22 in serum and sputum of stable chronic obstructive pulmonary disease patients. COPD. 10:459–465. 2013. View Article : Google Scholar : PubMed/NCBI
18	Yin Y, Hou G, Li E, Wang Q and Kang J: PPARγ agonists regulate tobacco smoke-induced Toll like receptor 4 expression in alveolar macrophages. Respir Res. 15:282014. View Article : Google Scholar : PubMed/NCBI
19	Strober W: Trypan blue exclusion test of cell viability. Curr Protoc Immunol. Appendix 3: Appendix 3B. 2001. View Article : Google Scholar
20	Au WW, Su D and Yuan J: Cigarette smoking in China: Public health, science and policy. Rev Environ Health. 27:43–49. 2012.PubMed/NCBI
21	Tilley AE, Harvey BG, Heguy A, et al: Down-regulation of the notch pathway in human airway epithelium in association with smoking and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 179:457–466. 2009. View Article : Google Scholar : PubMed/NCBI
22	Zheng Q, Qin H, Zhang H, et al: Notch signaling inhibits growth of the human lung adenocarcinoma cell line A549. Oncol Rep. 17:847–852. 2007.PubMed/NCBI
23	Kluk MJ, Ashworth T, Wang H, et al: Gauging NOTCH1 activation in cancer using immunohistochemistry. PLoS One. 8:e673062013. View Article : Google Scholar : PubMed/NCBI
24	Wael H, Yoshida R, Kudoh S, Hasegawa K, Niimori-Kita K and Ito T: Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma. Lung Cancer. 85:131–140. 2014. View Article : Google Scholar : PubMed/NCBI
25	Westhoff B, Colaluca IN, D'Ario G, et al: Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci USA. 106:22293–22298. 2009. View Article : Google Scholar : PubMed/NCBI
26	Foster JG, Wong SC and Sharp TV: The hypoxic tumor microenvironment: driving the tumorigenesis of non-small-cell lung cancer. Future Oncol. 10:2659–2674. 2014. View Article : Google Scholar : PubMed/NCBI
27	Graves EE, Maity A and Le QT: The tumor microenvironment in non-small-cell lung cancer. Semin Radiat Oncol. 20:156–163. 2010. View Article : Google Scholar : PubMed/NCBI
28	Maity A and Koumenis C: Location, location, location - makes all the difference for hypoxia in lung tumors. Clin Cancer Res. 16:4685–4687. 2010. View Article : Google Scholar : PubMed/NCBI
29	Chen Y, De Marco MA, Graziani I, et al: Oxygen concentration determines the biological effects of NOTCH-1 signaling in adenocarcinoma of the lung. Cancer Res. 67:7954–7959. 2007. View Article : Google Scholar : PubMed/NCBI
30	Eliasz S, Liang S, Chen Y, et al: Notch-1 stimulates survival of lung adenocarcinoma cells during hypoxia by activating the IGF-1R pathway. Oncogene. 29:2488–2498. 2010. View Article : Google Scholar : PubMed/NCBI
31	Baumgart A, Seidl S, Vlachou P, et al: ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non-small cell lung cancer. Cancer Res. 70:5368–5378. 2010. View Article : Google Scholar : PubMed/NCBI
32	Guo J, He L, Yuan P, et al: ADAM10 overexpression in human non-small cell lung cancer correlates with cell migration and invasion through the activation of the Notch1 signaling pathway. Oncol Rep. 28:1709–1718. 2012.PubMed/NCBI
33	Hsu YL, Wu CY, Hung JY, Lin YS, Huang MS and Kuo PL: Galectin-1 promotes lung cancer tumor metastasis by potentiating integrin α6β4 and Notch1/Jagged2 signaling pathway. Carcinogenesis. 34:1370–1381. 2013. View Article : Google Scholar : PubMed/NCBI
34	Zhang S, Long H, Yang YL, et al: Inhibition of CK2α down-regulates Notch1 signaling in lung cancer cells. J Cell Mol Med. 17:854–862. 2013. View Article : Google Scholar : PubMed/NCBI
35	Allen TD, Rodriguez EM, Jones KD and Bishop JM: Activated Notch1 induces lung adenomas in mice and cooperates with Myc in the generation of lung adenocarcinoma. Cancer Res. 71:6010–6018. 2011. View Article : Google Scholar : PubMed/NCBI
36	Zhou H, Luo Y, Chen JH, et al: Knockdown of TRB3 induces apoptosis in human lung adenocarcinoma cells through regulation of Notch1 expression. Mol Med Rep. 8:47–52. 2013.PubMed/NCBI
37	Ji X, Wang Z, Geamanu A, Sarkar FH and Gupta SV: Inhibition of cell growth and induction of apoptosis in non-small cell lung cancer cells by delta-tocotrienol is associated with notch-1 down-regulation. J Cell Biochem. 112:2773–2783. 2011. View Article : Google Scholar : PubMed/NCBI
38	Ji X, Wang Z, Geamanu A, Goja A, Sarkar FH and Gupta SV: Delta-tocotrienol suppresses Notch-1 pathway by upregulating miR-34a in nonsmall cell lung cancer cells. Int J Cancer. 131:2668–2677. 2012. View Article : Google Scholar : PubMed/NCBI
39	Ji X, Wang Z, Sarkar FH and Gupta SV: Delta-tocotrienol augments cisplatin-induced suppression of non-small cell lung cancer cells via inhibition of the Notch-1 pathway. Anticancer Res. 32:2647–2655. 2012.PubMed/NCBI
40	Xie M, He CS, Wei SH and Zhang L: Notch-1 contributes to epidermal growth factor receptor tyrosine kinase inhibitor acquired resistance in non-small cell lung cancer in vitro and in vivo. Eur J Cancer. 49:3559–3572. 2013. View Article : Google Scholar : PubMed/NCBI
41	Xie M, Zhang L, He CS, et al: Activation of Notch-1 enhances epithelial-mesenchymal transition in gefitinib-acquired resistant lung cancer cells. J Cell Biochem. 113:1501–1513. 2012.PubMed/NCBI
42	Liu YP, Yang CJ, Huang MS, et al: Cisplatin selects for multidrug-resistant CD133+ cells in lung adenocarcinoma by activating Notch signaling. Cancer Res. 73:406–416. 2013. View Article : Google Scholar : PubMed/NCBI
43	Yang Y, Yan X, Duan W, et al: Pterostilbene exerts antitumor activity via the Notch1 signaling pathway in human lung adenocarcinoma cells. PLoS One. 8:e626522013. View Article : Google Scholar : PubMed/NCBI
44	Liu J and Mao Z, Huang J, Xie S, Liu T and Mao Z: Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy. Biochem Biophys Res Commun. 444:670–675. 2014. View Article : Google Scholar : PubMed/NCBI
45	Dang TP, Gazdar AF, Virmani AK, et al: Chromosome 19 translocation, overexpression of Notch3 and human lung cancer. J Natl Cancer Inst. 92:1355–1357. 2000. View Article : Google Scholar : PubMed/NCBI
46	Konishi J, Kawaguchi KS, Vo H, et al: Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers. Cancer Res. 67:8051–8057. 2007. View Article : Google Scholar : PubMed/NCBI
47	Sullivan JP, Spinola M, Dodge M, et al: Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer Res. 70:9937–9948. 2010. View Article : Google Scholar : PubMed/NCBI
48	Weiss W: Cigarette smoke as a carcinogen. Am Rev Respir Dis. 108:364–366. 1973.PubMed/NCBI
49	Reif AE: Effect of cigarette smoking on susceptibility to lung cancer. Oncology. 38:76–85. 1981. View Article : Google Scholar : PubMed/NCBI