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Tumor Biology

, Volume 36, Issue 12, pp 9223–9231 | Cite as

Elevated expression of TGIF is involved in lung carcinogenesis

  • Yadong Wang
  • Haiyu Wang
  • Huiyan Gao
  • Bing Xu
  • Wenlong Zhai
  • Jiangmin Li
  • Congke Zhang
Research Article

Abstract

The purpose of this study was to explore the expression of TG-interacting factor (TGIF) in lung carcinogenesis. Malignant transformation of human bronchial epithelial (16HBE) cell was established by benzo(a)pyrene (BaP) treatment. Soft agar assay and tumor formation assay in nude mice were applied. Tumorigenesis experiment in vivo was done by BaP treatment. Western blotting, immunohistochemistry, and quantitative polymerase chain reaction were used to detect TGIF expression. We observed a higher level of TGIF messenger RNA (mRNA) in lung cancer tissues than that in paracancerous tissues. We observed significantly higher levels of TGIF mRNA and protein in A549 and H1299 cell lines than that in 16HBE cell. Increased expressions of TGIF protein and mRNA were observed in 16HBE cells induced by BaP treatment as compared to those in solvent control group. We observed significantly higher levels of TGIF mRNA and protein in 16HBE-BaP cells than that in 16HBE-control cells. We observed significantly higher levels of TGIF mRNA and protein in mice lung tissues treated with BaP than that in control group. Our results suggested that elevated expression of TGIF was involved in lung carcinogenesis.

Keywords

TGIF Lung carcinogenesis Benzo(a)pyrene Lung cancer 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (U1404815).

Conflicts of interest

None

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.CrossRefPubMedGoogle Scholar
  3. 3.
    Luqman M, Javed MM, Daud S, Raheem N, Ahmad J, Khan AU. Risk factors for lung cancer in the Pakistani population. Asian Pac J Cancer Prev. 2014;15:3035–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Phukan RK, Saikia BJ, Borah PK, Zomawia E, Sekhon GS, Mahanta J. Role of household exposure, dietary habits and glutathione S-transferases M1, T1 polymorphisms in susceptibility to lung cancer among women in Mizoram India. Asian Pac J Cancer Prev. 2014;15:3253–60.CrossRefPubMedGoogle Scholar
  5. 5.
    Zendehdel R, Tayefeh-Rahimian R, Kabir A. Chronic exposure to chlorophenol related compounds in the pesticide production workplace and lung cancer: a meta-analysis. Asian Pac J Cancer Prev. 2014;15:5149–53.CrossRefPubMedGoogle Scholar
  6. 6.
    van Loon AJ, Kant IJ, Swaen GM, Goldbohm RA, Kremer AM, van den Brandt PA. Occupational exposure to carcinogens and risk of lung cancer: results from The Netherlands cohort study. Occup Environ Med. 1997;54:817–24.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Risch A, Plass C. Lung cancer epigenetics and genetics. Int J Cancer. 2008;123:1–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Ridge CA, McErlean AM, Ginsberg MS. Epidemiology of lung cancer. Semin Intervent Radiol. 2013;30:93–8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Shames DS, Wistuba II. The evolving genomic classification of lung cancer. J Pathol. 2014;232:121–33.CrossRefPubMedGoogle Scholar
  10. 10.
    Cooper WA, Lam DC, O’Toole SA, Minna JD. Molecular biology of lung cancer. J Thorac Dis. 2013;5 Suppl 5:S479–490.PubMedPubMedCentralGoogle Scholar
  11. 11.
    D’Angelo SP, Pietanza MC. The molecular pathogenesis of small cell lung cancer. Cancer Biol Ther. 2010;10:1–10.CrossRefPubMedGoogle Scholar
  12. 12.
    He B, Barg RN, You L, Xu Z, Reguart N, Mikami I, et al. Wnt signaling in stem cells and non-small-cell lung cancer. Clin Lung Cancer. 2005;7:54–60.CrossRefPubMedGoogle Scholar
  13. 13.
    Wotton D, Lo RS, Lee S, Massague J. A Smad transcriptional corepressor. Cell. 1999;97:29–39.CrossRefPubMedGoogle Scholar
  14. 14.
    Bartholin L, Powers SE, Melhuish TA, Lasse S, Weinstein M, Wotton D. TGIF inhibits retinoid signaling. Mol Cell Biol. 2006;26:990–1001.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Yeh BW, Wu WJ, Li WM, Li CC, Huang CN, Kang WY, et al. Overexpression of TG-interacting factor is associated with worse prognosis in upper urinary tract urothelial carcinoma. Am J Pathol. 2012;181:1044–55.CrossRefPubMedGoogle Scholar
  16. 16.
    Borlak J, Meier T, Halter R, Spanel R, Spanel-Borowski K. Epidermal growth factor-induced hepatocellular carcinoma: gene expression profiles in precursor lesions, early stage and solitary tumours. Oncogene. 2005;24:1809–19.CrossRefPubMedGoogle Scholar
  17. 17.
    Castro M, Grau L, Puerta P, Gimenez L, Venditti J, Quadrelli S, et al. Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer. J Transl Med. 2010;8:86.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Pang Y, Li W, Ma R, Ji W, Wang Q, Li D, et al. Development of human cell models for assessing the carcinogenic potential of chemicals. Toxicol Appl Pharmacol. 2008;232:478–86.CrossRefPubMedGoogle Scholar
  19. 19.
    Wang Y, Cheng J, Li D, Duan H, Yang H, Bin P, et al. Modulation of DNA repair capacity by ataxia telangiectasia mutated gene polymorphisms among polycyclic aromatic hydrocarbons-exposed workers. Toxicol Sci. 2011;124:99–108.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhao P, Fu J, Yao B, Song Y, Mi L, Li Z, et al. In vitro malignant transformation of human bronchial epithelial cells induced by benzo(a)pyrene. Toxicol In Vitro. 2012;26:362–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhao Y, Liu H, Li Y, Wu J, Greenlee AR, Yang C, et al. The role of miR-506 in transformed 16HBE cells induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide. Toxicol Lett. 2011;205:320–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Chen Z, Zhang Y, Yang J, Jin M, Wang XW, Shen ZQ, et al. Estrogen promotes benzo[a]pyrene-induced lung carcinogenesis through oxidative stress damage and cytochrome c-mediated caspase-3 activation pathways in female mice. Cancer Lett. 2011;308:14–22.CrossRefPubMedGoogle Scholar
  23. 23.
    Bertolino E, Reimund B, Wildt-Perinic D, Clerc RG. A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif. J Biol Chem. 1995;270:31178–88.CrossRefPubMedGoogle Scholar
  24. 24.
    Pessah M, Prunier C, Marais J, Ferrand N, Mazars A, Lallemand F. c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity. Proc Natl Acad Sci U S A. 2001;98:6198–203.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Wotton D, Lo RS, Swaby LA, Massague J. Multiple modes of repression by the Smad transcriptional corepressor TGIF. J Biol Chem. 1999;274:37105–10.CrossRefPubMedGoogle Scholar
  26. 26.
    Seo SR, Lallemand F, Ferrand N, Pessah M, L’Hoste S, Camonis J, et al. The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation. EMBO J. 2004;23:3780–92.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Seo SR, Ferrand N, Faresse N, Prunier C, Abecassis L, Pessah M, et al. Nuclear retention of the tumor suppressor cPML by the homeodomain protein TGIF restricts TGF-beta signaling. Mol Cell. 2006;23:547–59.CrossRefPubMedGoogle Scholar
  28. 28.
    Gripp KW, Wotton D, Edwards MC, Roessler E, Ades L, Meinecke P, et al. Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination. Nat Genet. 2000;25:205–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Bartholin L, Melhuish TA, Powers SE, Goddard-Leon S, Treilleux I, Sutherland AE, et al. Maternal Tgif is required for vascularization of the embryonic placenta. Dev Biol. 2008;319:285–97.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Horie T, Ono K, Kinoshita M, Nishi H, Nagao K, Kawamura T, et al. TG-interacting factor is required for the differentiation of preadipocytes. J Lipid Res. 2008;49:1224–34.CrossRefPubMedGoogle Scholar
  31. 31.
    Nakakuki K, Imoto I, Pimkhaokham A, Fukuda Y, Shimada Y, Imamura M, et al. Novel targets for the 18p11.3 amplification frequently observed in esophageal squamous cell carcinomas. Carcinogenesis. 2002;23:19–24.CrossRefPubMedGoogle Scholar
  32. 32.
    Liborio TN, Ferreira EN, Aquino Xavier FC, Carraro DM, Kowalski LP, Soares FA, et al. TGIF1 splicing variant 8 is overexpressed in oral squamous cell carcinoma and is related to pathologic and clinical behavior. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116:614–25.CrossRefPubMedGoogle Scholar
  33. 33.
    Hamid R, Patterson J, Brandt SJ. Genomic structure, alternative splicing and expression of TG-interacting factor, in human myeloid leukemia blasts and cell lines. Biochim Biophys Acta. 2008;1779:347–55.CrossRefPubMedGoogle Scholar
  34. 34.
    Liu ZM, Tseng HY, Yeh BW, Wu WJ, Huang HS. TG-interacting factor mediates arsenic-induced malignant transformation of keratinocytes via c-Src/EGFR/AKT/FOXO3A and redox signalings. Arch Toxicol. 2014. doi: 10.1007/s00204-014-1445-x.PubMedCentralGoogle Scholar
  35. 35.
    Zerlanko BJ, Bartholin L, Melhuish TA, Wotton D. Premature senescence and increased TGFbeta signaling in the absence of Tgif1. PLoS One. 2012;7:e35460.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Liu ZM, Tseng JT, Hong DY, Huang HS. Suppression of TG-interacting factor sensitizes arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Biochem J. 2011;438:349–58.CrossRefPubMedGoogle Scholar
  37. 37.
    Liu ZM, Tseng HY, Cheng YL, Yeh BW, Wu WJ, Huang HS. TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis. Toxicol Appl Pharmacol. 2015. doi: 10.1016/j.taap.2015.03.007.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yadong Wang
    • 1
  • Haiyu Wang
    • 1
  • Huiyan Gao
    • 1
  • Bing Xu
    • 1
  • Wenlong Zhai
    • 2
  • Jiangmin Li
    • 1
  • Congke Zhang
    • 1
  1. 1.Department of ToxicologyHenan Center for Disease Control and PreventionZhengzhouChina
  2. 2.Department of General SurgeryFirst Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

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