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Tumor Biology

, Volume 35, Issue 4, pp 3455–3462 | Cite as

EMP1 regulates caspase-9 and VEGFC expression and suppresses prostate cancer cell proliferation and invasion

Research Article

Abstract

This study aimed to analyze the expression, clinical significance of f epithelial membrane protejn-1 (EMP-1) in prostate carcinoma, and the biological effect in its cell line by EMP1 overexpression. Immunohistochemistry and Western blot were used to analyze EMP1 protein expression in 76 cases of prostate cancer and 34 cases of normal tissues to study the relationship between EMP1 expression and clinical factors. EMP1 lentiviral vector and empty vector were respectively transfected into prostate cancer PC-3 cell line. Quantitative real-time reverse transcription polymerase chain reaction and Western blot were used to detect the mRNA level and protein of EMP1. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, migration, and invasion assays were also conducted as to the influence of the upregulated expression of EMP1 that might be found on PC-3 cell biological effect. Immunohistochemistry: The level of EMP1 protein expression was found to be significantly lower in prostate cancer tissue than normal tissues (P < 0.05). Western blot: The relative amount of EMP1 protein in prostate cancer tissue was found to be significantly lower than in normal tissues (P < 0.05). The level of EMP1 protein expression was not correlated with age and prostate-specific antigen (PSA) concentration (P > 0.05), but it was correlated with T stages, lymph node metastasis, clinic stage, and Gleason score (P < 0.05). The result of biological function shown that PC-3 cell transfected EMP1 had a lower survival fraction, higher cell apoptosis, significant decrease in migration and invasion, higher caspase-9, and lower VEGFC protein expression compared with PC-3 cell untransfected EMP1 (P < 0.05). EMP1 expression decreased in prostate cancer and correlated significantly T stages, lymph node metastasis, clinic stage, and Gleason score, suggesting that EMP1 may play important roles as a negative regulator to prostate cancer PC-3 cell by regulating the expression of regulation of caspase-9 and VEGFC protein.

Key words

EMP1 Prostate carcinoma Caspase-9 VEGFC Metastasis Prognosis 

Notes

Conflicts of interest

None

Reference

  1. 1.
    Greenlee RT, Murray T, Bolden S, Wingo PA, Cancer statistics. CA CancerJ Clin. 2000;50:7–33.CrossRefGoogle Scholar
  2. 2.
    Dong JT, Isaacs WB, Isaacs JT. Molecular advances in prostate cancer. Curr opin oncol. 1997;9:101–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Lai S, Wang G, Cao X, Li Z, Hu J, Wang J. EMP-1 promotes tumorigenesis of NSCLC through PI3K/AKT pathway. J Huazhong Univ Sci Technolog Med Sci. 2012;32:834–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Taylor V, Welcher AA, Program AE, Suter U. Epithelial membrane protein-1, peripheral myelin protein 22, and lens membrane protein 20 define a novel gene family. J Biol Chem. 1995;270:28824–33.PubMedCrossRefGoogle Scholar
  5. 5.
    Lobsiger CS, Magyar JP, Taylor V, Wulf P, Welcher AA, Program AE, et al. Identification and characterization of a cDNA and the structural gene encoding the mouse epithelial membrane protein-1. Genomics. 1996;36:379–87.PubMedCrossRefGoogle Scholar
  6. 6.
    Wulf P, Suter U. Embryonic expression of epithelial membrane protein 1 in early neurons. Brain Res Dev Brain Res. 1999;116:169–80.PubMedCrossRefGoogle Scholar
  7. 7.
    Zoidl G, Blass-Kampmann S, D'Urso D, Schmalenbach C, Müller HW. Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in Schwann cells: modulation of cell growth. EMBO J. 1995;14:1122–8.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Jetten AM, Suter U. The peripheral myelin protein 22 and epithelial membrane protein family. Prog Nucleic Acid Res Mol Biol. 2000;64:97–129.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee HS, Sherley JL, Chen JJ, Chiu CC, Chiou LL, Liang JD, et al. EMP1 is a junctional protein in a liver stem cell line and in the liver. Biochem Biophys res commun. 2005;334:996–1003.PubMedCrossRefGoogle Scholar
  10. 10.
    Gnirke AU, Weidle UH. Investigation of prevalence and regulation of expression of progression associated protein (PAP). Anticancer Res. 1998;18:4363–9.PubMedGoogle Scholar
  11. 11.
    Wang HT, Kong JP, Ding F, Wang XQ, Wang MR, Liu LX, et al. Analysis of gene expression profile induced by EMP-1 inesophageal cancer cells using cDNA microarray. World J Gastroenterol. 2003;9:392–8.PubMedGoogle Scholar
  12. 12.
    Zhang J, Cao W, Xu Q, Chen WT. The expression of EMP1 is downregulated in oral squamous cell carcinoma and possibly associated with tumour metastasis. J Clin Pathol. 2011;64:25–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Fu L, Chen W, Guo W, Wang J, Tian Y, Shi D, et al. Berberine targets AP-2/hTERT, NF-κB/COX-2, HIF-1α/VEGF and cytochrome-c/caspase signaling to suppress human cancer cell growth. PLoS One. 2013;8:e69240.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Sen S, Kawahara B, Chaudhuri G. Mitochondrial-associated nitric oxide synthase activity inhibits cytochrome c oxidase: implications for breast Cancer. Free Radic Biol Med. 2013;57:210–20.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhang JM, Wang HC, Wang HX, Ruan LH, Zhang YM, Li JT, et al. Oxidative stress and activities of caspase-8,-9,and −3 are involved in cryopreservation- induced apoptosis ingranulosa cells. Eur J Obstet Gynecol Reprod Biol. 2013;166:52–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Peng J, Shao N, Peng H, Chen LQ. Prognostic significance of vascular endothelial growth factor expression in esophageal carcinoma: a meta-analysis. J Buon. 2013;18:398–406.PubMedGoogle Scholar
  17. 17.
    Xie LX, Zhai TT, Yang LP, Yang E, Zhang XH, Chen JY, et al. Lymphangiogenesis and prognostic significance of vascular endothelial growth factor C in gastro-oesophageal junction adenocarcinoma. Int J Exp Pathol. 2013;94:39–46.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of ChemoradiotherapyTangshan People’s HospitalTangshanChina
  2. 2.Department of RadiotherapyThe Military General Hospital of Beijing PLABeijingChina
  3. 3.Department of UrologyTangshan Workers HospitalTangshanChina
  4. 4.Department of RadiotherapyThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

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