Skip to main content

Advertisement

SpringerLink
Log in

PEBP4 enhanced HCC827 cell proliferation and invasion ability and inhibited apoptosis

  • Research Article
  • Published:
Tumor Biology

Abstract

The purposes of this study were to investigate the effects of phosphatidylethanolamine-binding protein 4 (PEBP4) on the cell growth, proliferation, apoptosis, and invasion of non-small cell lung cancer (NSCLC) cells and to provide evidence for future treatment options for NSCLC. Western blot assays were performed to examine PEBP4 protein expression levels in NSCLC cell lines (HCC827, A549, NCI-H661, NCI-H292, and 95-D) and a normal human bronchial epithelial (HBE) cell line. A PEBP4 shRNA expression vector was constructed and transfected into HCC827 cells. Subsequently, the effects of PEBP4 on the cell viability, cell cycle distribution, apoptosis levels, and invasion properties of HCC827 cells were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry analyses, and transwell invasion assays. In addition, the effects of PEBP4 on the expression of proteins including cyclin D1, p53, Bcl-2, MMP-2, and MMP-9 were investigated. PEBP4 was highly expressed in lung cancer cells (HCC827, A549, NCI-H661, NCI-H292, and 95-D), but its expression was low in HBE cells. Cell viability, cell proliferation, and invasion of HCC827 cells in the PEBP4 knockdown group were significantly lower than that in the negative control and blank control groups (p < 0.05), and there were no significant differences between the negative and blank control groups in terms of cell viability, cell proliferation, apoptosis, and invasion. In HCC827 cells, the expression levels of cyclin D1, Bcl-2, MMP-2, and MMP-9 in the PEBP4 knockdown group were significantly lower (p < 0.05), and the expression of p53 protein was significantly higher than that in the negative and blank control groups (p < 0.05). There were no significant differences between the negative and blank control groups in the expression levels of cyclin D1, p53, Bcl-2, MMP-2, and MMP-9. In conclusion, PEBP4 enhanced HCC827 cell proliferation and invasion ability and inhibited apoptosis. Decreased PEBP4 expression may play a role in the reduced invasion ability and increased apoptosis of the human NSCLC cell line HCC827.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Reference

  1. Ellis PM, Vandermeer R. Delays in the diagnosis of lung cancer. J Thorac Dis. 2011;3(3):183–8.

    PubMed  Google Scholar 

  2. Hennon MW, Demmy TL. Video-assisted thoracoscopic surgery (VATS) for locally advanced lung cancer. Ann Cardiothorac Surg. 2012;1(1):37–42.

    Google Scholar 

  3. Tanner NT, Sherman CA, Silvestri GA. Biomarkers in the selection of maintenance therapy in non-small cell lung cancer. Transl Lung Cancer Res. 2012;1(2):96–8.

    Google Scholar 

  4. Bernier I, Jolles P. Purification and characterization of a basic 23 kDa cytosolic protein from bovine brain. Biochim Biophys Acta. 1984;790(2):174–81.

    Article  PubMed  CAS  Google Scholar 

  5. Garcia R, Grindlay J, Rath O, Fee F, Kolch W. Regulation of human myoblast differentiation by PEBP4. EMBO Rep. 2009;10(3):278–84.

    Article  PubMed  CAS  Google Scholar 

  6. Su XL, Bin B, Cui HW, Ran MR. Cytochrome P450 2E1 RsaI/PstI and DraI polymorphisms are risk factors for lung cancer in Mongolian and Han population in Inner Mongolia. Chin J Cancer Res. 2011;23(2):107–11.

    Article  CAS  Google Scholar 

  7. Yang P, Xu XY, Liu XJ, Gong JS. The value of delayed 18 F FDG-PET imaging in diagnosis of solitary pulmonary nodules: a preliminary study on 28 patients. Quant Imaging Med Surg. 2011;1:31–4.

    PubMed  CAS  Google Scholar 

  8. Cheng GC, Chen DT, Chen JJ, Soong SJ, Lamartiniere CA, Barnes S. A chain reaction approach to modelling gene pathways. Transl Cancer Res. 2012;1(2):61–73.

    PubMed  Google Scholar 

  9. Kikuchi R, Kawahigashi H, Ando T, Tonooka T, Handa H. Molecular and functional characterization of PEBP genes in barley reveal the diversification of their roles in flowering. Plant Physiol. 2009;149(3):1341–53.

    Article  PubMed  CAS  Google Scholar 

  10. Odabaei G, Chatterjee D, Jazirehi AR, Goodglick L, Yeung K, Bonavida B. Raf-1 kinase inhibitor protein: structure, function, regulation of cell signaling, and pivotal role in apoptosis. Adv Cancer Res. 2004;91:169–200.

    Article  PubMed  CAS  Google Scholar 

  11. Yeung K, Seitz T, Li S, Janosch P, McFerran B, Kaiser C, et al. Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature. 1999;401(6749):173–7.

    Article  PubMed  CAS  Google Scholar 

  12. Corbit KC, Trakul N, Eves EM, Diaz B, Marshall M, Rosner MR. Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein. J Biol Chem. 2003;278(15):13061–8.

    Article  PubMed  CAS  Google Scholar 

  13. Shemon AN, Heil GL, Granovsky AE, Clark MM, McElheny D, Chimon A, et al. Characterization of the Raf kinase inhibitory protein (RKIP) binding pocket: NMR-based screening identifies small-molecule ligands. PLoS One. 2010;5(5):e10479.

    Article  PubMed  Google Scholar 

  14. Zaravinos A, Chatziioannou M, Lambrou GI, Boulalas I, Delakas D, Spandidos DA. Implication of RAF and RKIP genes in urinary bladder cancer. Pathol Oncol Res. 2011;17(2):181–90.

    Article  PubMed  CAS  Google Scholar 

  15. Wang X, Li N, Liu B, Sun H, Chen T, Li H, et al. A novel human phosphatidylethanolamine-binding protein resists tumor necrosis factor alpha-induced apoptosis by inhibiting mitogen-activated protein kinase pathway activation and phosphatidylethanolamine externalization. J Biol Chem. 2004;279(44):45855–64.

    Article  PubMed  CAS  Google Scholar 

  16. Qiu J, Xiao J, Han C, Li N, Shen X, Jiang H, et al. Potentiation of tumor necrosis factor-alpha-induced tumor cell apoptosis by a small molecule inhibitor for anti-apoptotic protein hPEBP4. J Biol Chem. 2010;285(16):12241–7.

    Article  PubMed  CAS  Google Scholar 

  17. Liu H, Qiu J, Li N, Chen T, Cao X. Human phosphatidylethanolamine-binding protein 4 promotes transactivation of estrogen receptor alpha (ERalpha) in human cancer cells by inhibiting proteasome-dependent ERalpha degradation via association with Src. J Biol Chem. 2010;285(29):21934–42.

    Article  PubMed  CAS  Google Scholar 

  18. Yu GP, Huang B, Chen GQ, Wu S, Ji Y, Shen ZY. PEBP4 gene expression and its significance in invasion and metastasis of non-small cell lung cancer. Tumour Biol. 2012;33(1):223–8.

    Article  PubMed  CAS  Google Scholar 

  19. Yu GP, Chen GQ, Wu S, Shen K, Ji Y. The expression of PEBP4 protein in lung squamous cell carcinoma. Tumour Biol. 2011;32(6):1257–63.

    Article  PubMed  CAS  Google Scholar 

  20. Wang X, Li N, Li H, Liu B, Qiu J, Chen T, et al. Silencing of human phosphatidylethanolamine-binding protein 4 sensitizes breast cancer cells to tumor necrosis factor-alpha-induced apoptosis and cell growth arrest. Clin Cancer Res. 2005;11(20):7545–53.

    Article  PubMed  CAS  Google Scholar 

  21. Li P, Wang X, Li N, Kong H, Guo Z, Liu S, et al. Anti-apoptotic hPEBP4 silencing promotes TRAIL-induced apoptosis of human ovarian cancer cells by activating ERK and JNK pathways. Int J Mol Med. 2006;18(3):505–10.

    PubMed  CAS  Google Scholar 

  22. Zhang Y, Wang X, Xiang Z, Li H, Qiu J, Sun Q, et al. Promotion of cellular migration and apoptosis resistance by a mouse eye-specific phosphatidylethanolamine-binding protein. Int J Mol Med. 2007;19(1):55–63.

    PubMed  Google Scholar 

  23. Liu H, Kong Q, Li B, He Y, Li P, Jia B. Expression of PEBP4 protein correlates with the invasion and metastasis of colorectal cancer. Tumour Biol. 2012;33(1):267–73.

    Article  PubMed  Google Scholar 

  24. Li H, Wang X, Li N, Qiu J, Zhang Y, Cao X. hPEBP4 resists TRAIL-induced apoptosis of human prostate cancer cells by activating Akt and deactivating ERK1/2 pathways. J Biol Chem. 2007;282(7):4943–50.

    Article  PubMed  CAS  Google Scholar 

  25. Kim D, Kim S, Koh H, Yoon SO, Chung AS, Cho KS, et al. Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J. 2001;15(11):1953–62.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, No. 188, Shi Zi Rd., Soochow, 215006, People’s Republic of China

    Guiping Yu, Zhenya Shen, Xiaomei Teng & Yanqiu Hu

  2. Department of Cardiothoracic Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, China

    Guoqiang Chen & Bin Huang

Authors
  1. Guiping Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhenya Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guoqiang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaomei Teng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanqiu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhenya Shen.

Additional information

Guiping Yu and Guoqiang Chen contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, G., Shen, Z., Chen, G. et al. PEBP4 enhanced HCC827 cell proliferation and invasion ability and inhibited apoptosis. Tumor Biol. 34, 91–98 (2013). https://doi.org/10.1007/s13277-012-0514-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0514-0

Keywords

Search

Navigation