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November 2013 Volume 8 Issue 5

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Article

Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100

  • Authors:
    • Yue Ren
    • Qiong Wu
    • Yafang Liu
    • Xiaoming Xu
    • Chengshi Quan
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Pathobiology, Ministry of Education, Bethune Medical College, Jilin University, Changchun, Jilin 130021, P.R. China
  • Pages: 1505-1510
    |
    Published online on: September 10, 2013
       https://doi.org/10.3892/mmr.2013.1675
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Abstract

Disruption or loss of tight junction structure and function is associated with tumor growth, invasion and metastasis in tumors of human epithelial origin. Since claudin is the most important backbone protein of tight junctions, the downregulation or loss of claudin expression is hypothesized to be important for tumor development and metastasis. In the current study, RNA interference (RNAi) was used to knock down the expression of claudin‑6 to investigate the effect of claudin‑6 downregulation on the malignant phenotype in the human breast epithelium cell line HBL‑100. The junctional function was investigated by measuring the transepithelial electrical resistance across the confluent epithelial cell layer. Manual cell counting and wound healing assays were performed to examine cell proliferation and migration. Changes in matrix metalloproteinase‑2 (MMP‑2) expression and activity were examined by reverse transcription polymerase chain reaction (RT‑PCR) and gelatin zymography. The expression of p38 mitogen‑activated protein kinases (MAPKs) and phosphorylated p38 MAPK were measured by western blot analysis. Claudin‑6 knockdown resulted in significantly lower transepithelial electrical resistance (P<0.001), higher growth rate (P<0.001) and migratory ability (P<0.001) accompanied with an increased MMP‑2 expression and activity (P<0.001). Furthermore, a decreased expression of phosphorylated p38 MAPK (P<0.001) was detected in HBL‑100 cells. These observations support the hypothesis that a decreased expression of claudin‑6 contributes to the malignant progression of human breast cancer.
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1 

Elkouby-Naor L and Ben-Yosef T: Functions of claudin tight junction proteins and their complex interactions in various physiological systems. Int Rev Cell Mol Biol. 279:1–32. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Tsukita S, Furuse M and Itoh M: Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2:285–293. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Matter K, Aijaz S, Tsapara A and Balda MS: Mammalian tight junctions in the regulation of epithelial differentiation and proliferation. Curr Opin Cell Biol. 17:453–458. 2005. View Article : Google Scholar : PubMed/NCBI

4 

González-Mariscal L, Betanzos A, Nava P and Jaramillo BE: Tight junction proteins. Prog Biophys Mol Biol. 81:1–44. 2003.

5 

Takahashi A, Kondoh M, Kodaka M and Yagi K: Peptides as tight junction modulators. Curr Pharm Des. 17:2699–2703. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Lee KW, Lee NK, Kim JH, et al: Twist1 causes the transcriptional repression of claudin-4 with prognostic significance in esophageal cancer. Biochem Biophys Res Commun. 423:454–460. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Tokés AM, Kulka J, Paku S, et al: Claudin-1, -3, and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res. 7:R296–R305. 2005.PubMed/NCBI

8 

Miyamori H, Takino T, Kobayashi Y, Tokai H, Itoh Y, Seiki M and Sato H: Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. J Biol Chem. 276:28204–28211. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Turksen K and Troy TC: Junctions gone bad: claudins and loss of the barrier in cancer. Biochim Biophys Acta. 1816:73–79. 2011.PubMed/NCBI

10 

Quan C and Lu SJ: Identification of genes preferentially expressed in mammary epithelial cells of Copenhagen rat using subtractive hybridization and microarrays. Carcinogenesis. 24:1593–1599. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Wu Q, Liu Y, Ren Y, Xu X, Yu L, Li Y and Quan C: Tight junction protein, claudin-6, downregulates the malignant phenotype of breast carcinoma. Eur J Cancer Prev. 19:186–194. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Hui L, Bakiri L, Stepniak E and Wagner EF: p38alpha: a suppressor of cell proliferation and tumorigenesis. Cell Cycle. 6:2429–2433. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Green JA, Dholakia S, Friedland JS, et al: Mycobacterium tuberculosis-infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNFα, NFκB, p38 and caspase 8 dependent pathways. J Neuroinflammation. 8:462011.PubMed/NCBI

14 

Kim ES, Kim MS and Moon A: TGF-beta-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. Int J Oncol. 25:1375–1382. 2004.PubMed/NCBI

15 

Hazan RB, Qiao R, Keren R, Badano I and Suyama K: Cadherin switch in tumor progression. Ann NY Acad Sci. 1014:155–163. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Jordan NV, Johnson GL and Abell AN: Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle. 10:2865–2873. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Bhat AA, Sharma A, Pope J, Krishnan M, Washington MK, Singh AB and Dhawan P: Caudal homeobox protein cdx-2 cooperates with Wnt pathway to regulate claudin-1 expression in colon cancer cells. PLoS One. 7:e371742012. View Article : Google Scholar : PubMed/NCBI

18 

Neesse A, Griesmann H, Gress TM and Michl P: Claudin-4 as therapeutic target in cancer. Arch Biochem Biophys. 524:64–70. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Lambert D, Padfield PJ, McLaughlin J, Cannell S and O’Neill CA: Ochratoxin A displaces claudins from detergent resistant membrane microdomains. Biochem Biophys Res Commun. 358:632–636. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Haorah J, Heilman D, Persidsky Y, et al: Ethanol-induced activation of myosin light chain kinase leads to dysfunction of tight junctions and blood-brain barrier compromise. Alcohol Clin Exp Res. 29:999–1009. 2005. View Article : Google Scholar

21 

Oshima T, Miwa H and Joh T: Aspirin induces gastric epithelial barrier dysfunction by activating p38 MAPK via claudin-7. Am J Physiol Cell Physiol. 295:C800–C806. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Li Q, Zhu F and Chen P: miR-7 and miR-218 epigenetically control tumor suppressor genes RASSF1A and Claudin-6 by targeting HoxB3 in breast cancer. Biochem Biophys Res Commun. 424:28–33. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Sun C, Yi T, Song X, et al: Efficient inhibition of ovarian cancer by short hairpin RNA targeting claudin-3. Oncol Rep. 26:193–200. 2011.PubMed/NCBI

24 

Hui L, Bakiri L, Mairhorfer A, et al: p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway. Nat Genet. 39:741–749. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Perdiguero E, Ruiz-Bonilla V, Gresh L, et al: Genetic analysis of p38 MAP kinases in myogenesis: fundamental role of p38alpha in abrogating myoblast proliferation. EMBO J. 26:1245–1256. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Ventura JJ, Tenbaum S, Perdiguero E, Huth M, Guerra C, Barbacid M, Pasparakis M and Nebreda AR: p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet. 39:750–758. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Bulavin DV and Fornace AJ Jr: p38 MAP kinase’s emerging role as a tumor suppressor. Adv Cancer Res. 92:95–118. 2004.

28 

Lee B, Kim CH and Moon SK: Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through inducing p38 mitogen activated protein kinase in vascular smooth muscle cells. FEBS Lett. 580:5177–5184. 2006. View Article : Google Scholar

29 

Takehara M, Nishimura T, Mima S, Hoshino T and Mizushima T: Effect of claudin expression on paracellular permeability, migration and invasion of colonic cancer cells. Biol Pharm Bull. 32:825–831. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Ikari A, Takiguchi A, Atomi K, Sato T and Sugatani J: Decrease in claudin-2 expression enhances cell migration in renal epithelial Madin-Darby canine kidney cells. J Cell Physiol. 226:1471–1478. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Osanai M, Murata M, Chiba H, Kojima T and Sawada N: Epigenetic silencing of claudin-6 promotes anchorage-independent growth of breast carcinoma cells. Cancer Sci. 98:1557–1562. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Agarwal R, D’Souza T and Morin PJ: Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res. 65:7378–7385. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ren Y, Wu Q, Liu Y, Xu X and Quan C: Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100. Mol Med Rep 8: 1505-1510, 2013.
APA
Ren, Y., Wu, Q., Liu, Y., Xu, X., & Quan, C. (2013). Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100. Molecular Medicine Reports, 8, 1505-1510. https://doi.org/10.3892/mmr.2013.1675
MLA
Ren, Y., Wu, Q., Liu, Y., Xu, X., Quan, C."Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100". Molecular Medicine Reports 8.5 (2013): 1505-1510.
Chicago
Ren, Y., Wu, Q., Liu, Y., Xu, X., Quan, C."Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100". Molecular Medicine Reports 8, no. 5 (2013): 1505-1510. https://doi.org/10.3892/mmr.2013.1675
Copy and paste a formatted citation
x
Spandidos Publications style
Ren Y, Wu Q, Liu Y, Xu X and Quan C: Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100. Mol Med Rep 8: 1505-1510, 2013.
APA
Ren, Y., Wu, Q., Liu, Y., Xu, X., & Quan, C. (2013). Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100. Molecular Medicine Reports, 8, 1505-1510. https://doi.org/10.3892/mmr.2013.1675
MLA
Ren, Y., Wu, Q., Liu, Y., Xu, X., Quan, C."Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100". Molecular Medicine Reports 8.5 (2013): 1505-1510.
Chicago
Ren, Y., Wu, Q., Liu, Y., Xu, X., Quan, C."Gene silencing of claudin‑6 enhances cell proliferation and migration accompanied with increased MMP‑2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL‑100". Molecular Medicine Reports 8, no. 5 (2013): 1505-1510. https://doi.org/10.3892/mmr.2013.1675
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