Comparative Proteomics of Chromium-Transformed Beas-2B Cells by 2D-DIGE and MALDI-TOF/TOF MS
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Chromium (Cr) is a highly toxic, common heavy metal used in industrial production. There are two types of Cr in nature: hexavalent chromium (Cr(VI)) and chromium trichloride (Cr(III)). Cr(III) is involved in the metabolism of sugars and lipids, whereas Cr(VI) is absorbed through the respiratory tract and skin and generates free radicals that result in secondary toxicity. Cr(VI) leads to cancer in the occupational population and is therefore recognized as a human carcinogen by the International Agency for Research on Cancer. The specific mechanism underlying Cr-induced carcinogenesis is complex. In this study, two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight/time-of-flight mass spectrometry-based techniques were performed to analyze differentially expressed proteins between Beas-2B human bronchial epithelial cells and Cr(VI)-transformed Beas-2B cells. Many differentially expressed proteins were identified in the cells after malignant transformation, including serine/threonine kinase 11, endothelial nitric oxide synthase 3, apolipoprotein A1, vinculin, and lamin A/C. These proteins are involved in many signaling and metabolic pathways, including apoptosis, autophagy, the PI3K/Akt signaling pathway, focal adhesion, cell motility, and actin cytoskeleton rearrangement.
KeywordsChromium Immortalized normal human bronchial epithelial cells Transformation Lung cancer 2D-DIGE MALDI TOF/TOF MS
This work was supported by grants from the National Natural Science Foundation of China (No. 31271272) and the Nanjing 321 Plan (No. 2013A12001). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
Compliance with Ethical Standards
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
- 1.Seidler A, Jahnichen S, Hegewald J et al. (2013) Reply to: Pesch B, Weiss T, Pallapies D, Schluter G, Bruning T. Letter to the editor. Re: Seidler A, Jahnichen S, Hegewald J, Fishta A, Krug O, Ruter L, Strik C, Hallier E, Straube S. Systematic review and quantification of respiratory cancer risk for occupational exposure to hexavalent chromium. Int Arch Occup Environ Health 86:961–963, 8, DOI: https://doi.org/10.1007/s00420-013-0888-3
- 4.Arita A, Costa M (2009) Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium. Metallomics: integrated biometal science 1:222–228Google Scholar
- 5.Matthews JO, Southern LL, Fernandez JM, Pontif JE, Bidner TD, Odgaard RL (2001) Effect of chromium picolinate and chromium propionate on glucose and insulin kinetics of growing barrows and on growth and carcass traits of growing-finishing barrows. J Anim Sci 79(8):2172–2178. https://doi.org/10.2527/2001.7982172x CrossRefPubMedGoogle Scholar
- 7.Tossavainen A (1990) Estimated risk of lung cancer attributable to occupational exposures in iron and steel foundries. IARC Sci Publ:363–367Google Scholar
- 8.Morgensztern D, Ng SH, Gao F et al (2010) Trends in stage distribution for patients with non-small cell lung cancer: a National Cancer Database Survey. J Thorac Oncol Off Publ Int Assoc Stud Lung Cancer 5:29–33Google Scholar
- 10.Ettinger DS, Akerley W, Borghaei H et al. (2012) Non-small cell lung cancer. J Natl Compr Canc Netw Jnccn 10:1236Google Scholar
- 14.Sakthivel KM, Sehgal P (2016) A novel role of lamins from genetic disease to cancer biomarkers. Oncol Rev 10(2). https://doi.org/10.4081/oncol.2016.309
- 15.Shimi T, Pfleghaar K, S, Pack C et al. (2008) The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. Genes Dev 22:3409, 24, 3421, DOI: https://doi.org/10.1101/gad.1735208
- 18.Kaspi E, Frankel D, Guinde J, Perrin S, Laroumagne S, Robaglia-Schlupp A, Ostacolo K, Harhouri K, Tazi-Mezalek R, Micallef J, Dutau H, Tomasini P, de Sandre-Giovannoli A, Lévy N, Cau P, Astoul P, Roll P (2017) Low lamin A expression in lung adenocarcinoma cells from pleural effusions is a pejorative factor associated with high number of metastatic sites and poor performance status. PLoS One 12(8):e0183136. https://doi.org/10.1371/journal.pone.0183136 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Kim D, Dai J, Yenwong FL et al (2015) Constitutive activation of epidermal growth factor receptor promotes tumorigenesis of Cr(VI)-transformed cells through decreased reactive oxygen species and apoptosis resistance development. J Biol Chem 290(4):2213–2224. https://doi.org/10.1074/jbc.M114.619783 CrossRefPubMedGoogle Scholar
- 24.Yan HJ, Tan Y, Gu W (2014) Neuron specific enolase and prognosis of non-small cell lung cancer: a systematic review and meta-analysis. J BUON: Off J Balkan Union Oncol 19:153–156Google Scholar
- 30.Thakur RK, Yadav VK, Kumar A, Singh A, Pal K, Hoeppner L, Saha D, Purohit G, Basundra R, Kar A, Halder R, Kumar P, Baral A, Kumar MJM, Baldi A, Vincenzi B, Lorenzon L, Banerjee R, Kumar P, Shridhar V, Mukhopadhyay D, Chowdhury S (2014) Non-metastatic 2 (NME2)-mediated suppression of lung cancer metastasis involves transcriptional regulation of key cell adhesion factor vinculin. Nucleic Acids Res 42(18):11589–11600. https://doi.org/10.1093/nar/gku860 CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Tada A, Kato H, Takenaga K, Hasegawa S (1997) Transforming growth factor beta1 increases the expressions of high molecular weight tropomyosin isoforms and vinculin and suppresses the transformed phenotypes in human lung carcinoma cells. Cancer Lett 121(1):31–37. https://doi.org/10.1016/S0304-3835(97)00319-4 CrossRefPubMedGoogle Scholar
- 32.Gill RK, Yang SH, Meerzaman D, Mechanic LE, Bowman ED, Jeon HS, Roy Chowdhuri S, Shakoori A, Dracheva T, Hong KM, Fukuoka J, Zhang JH, Harris CC, Jen J (2011) Frequent homozygous deletion of the LKB1/STK11 gene in non-small cell lung cancer. Oncogene 30(35):3784–3791. https://doi.org/10.1038/onc.2011.98 CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Ekizoglu S, Dogan S, Ulker D, Seven D, Gozen ED, Karaman E, Buyru N (2015) The effect of LKB1 on the PI3K/Akt pathway activation in association with PTEN and PIK3CA in HNC. Clin Otolaryngolog: Off J ENT-UK; Off J Netherlands Soc Oto-Rhino-Laryngol Cervico-Facial Surg 40(6):622–628. https://doi.org/10.1111/coa.12427 CrossRefGoogle Scholar
- 36.Liu K, Luo Y, Tian H, Yu KZ, He JX, Shen WY (2014) The tumor suppressor LKB1 antagonizes WNT signaling pathway through modulating GSK3β activity in cell growth of esophageal carcinoma. Tumour Biol J Int Soc Oncodev Biol Med 35(2):995–1002. https://doi.org/10.1007/s13277-013-1133-0 CrossRefGoogle Scholar