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Smad4 mediates malignant behaviors of human ovarian carcinoma cell through the effect on expressions of E-cadherin, plasminogen activator inhibitor-1 and VEGF

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Smad4 is involved in cancer progression and metastasis. Using a pair of human syngeneic epithelial ovarian cancer cells with low (HO-8910) and high (HO-8910PM) metastatic abilities, we aimed to reveal the role of Smad4 in ovarian cancer metastasis in vitro. Smad4 was down-regulated in HO-8910PM cell line relative to HO-8910 by implicating Smad4 was probably a potential tumor suppressor gene for ovarian cancer. Re-expression of Smad4 decreased the migration ability and inhibited the invasion capacity of HO-8910PM, while promoted the cell adhesion capacity for HO-8910PM. The stable expression of Smad4 increased the expression of E-cadherin, reduced the expression of plasminogen activator inhibitor-1(PAI-1) and slightly down-regulated the expression of VEGF. Smad4 suppresses human ovarian cancer cell metastasis potential through its effect on the expressions of PAI-1, E-cadherin and VEGF. Results from current work implicate Smad4might suppress the invasion and metastasis of human ovarian tumor cells through a TGF-β/Smad-mediated pathway.

Abstract

Smad4 is involved in cancer progression and metastasis. Using a pair of human syngeneic epithelial ovarian cancer cells with low (HO-8910) and high (HO-8910PM) metastatic abilities, we aimed to reveal the role of Smad4 in ovarian cancer metastasis in vitro. Smad4 was down-regulated in HO-8910PM cell line relative to HO-8910 by implicating Smad4 was probably a potential tumor suppressor gene for ovarian cancer. Re-expression of Smad4 decreased the migration ability and inhibited the invasion capacity of HO-8910PM, while promoted the cell adhesion capacity for HO-8910PM. The stable expression of Smad4 increased the expression of E-cadherin, reduced the expression of plasminogen activator inhibitor-1(PAI-1) and slightly down-regulated the expression of VEGF. Smad4 suppresses human ovarian cancer cell metastasis potential through its effect on the expressions of PAI-1, E-cadherin and VEGF. Results from current work implicate Smad4might suppress the invasion and metastasis of human ovarian tumor cells through a TGF-β/Smad-mediated pathway.

참고문헌 (30)

  1. Ouyang, G., "Genistein induces G2", M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways, 2009, pp.33, 1237~1244
  2. Zhang, Y., "PGC-1alpha induces apoptosis in human epithelial ovarian cancer cells through a PPARgamma-dependent pathway", Cell Res., 17, pp.363~373 (2007)
  3. Jemal, A., "Cancer statistics, 2002", CA. Cancer J. Clin., 52, pp.23~47 (2002)
  4. Zhang, L., "Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer", N. Engl. J. Med., 348, pp.203~213 (2003)
  5. Wooster, R., "Breast and ovarian cancer", N. Engl. J. Med., 348, pp.2339~2347 (2003)
  6. Hahn, S. A., "DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1", Science, 271, pp.350~353 (1996)
  7. Inman, G. J., "Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity", Mol. Cell, 10, pp.283~294 (2002)
  8. Moustakas, A., "Smad regulation in TGF-beta signal transduction", J. Cell Sci., 114, pp.4359~4369 (2001)
  9. Muller, N., "Smad4 induces the tumor suppressor E-cadherin and P-cadherin in colon carcinoma cells", Oncogene, 21, pp.6049~6058 (2002)
  10. Losi, L., "Loss of Smad4 expression predicts liver metastasis in human colorectal cancer", Oncol. Rep., 17, pp.1095~1099 (2007)
  11. Zhao, S., "Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells", Cancer Res., 68, pp.4221~4228 (2008)
  12. Ke, Z., "Expression of DPC4", Smad4 in non-small-cell lung carcinoma and its relationship with angiogenesis, 2008, pp.55, 323~329
  13. Sunde, J. S., "Expression profiling identifies altered expression of genes that contribute to the inhibition of transforming growth factor-beta signaling in ovarian cancer", Cancer Res., 66, pp.8404~8412 (2006)
  14. Shenhua, X., "Establishment of a highly metastatic human ovarian cancer cell line (HO-8910PM) and its characterization", J. Exp. Clin. Cancer Res., 18, pp.233~239 (1999)
  15. Shi, J., "Effect of hypoxia and re-oxygenation on cell invasion and adhesion in human ovarian carcinoma cells", Oncol. Rep., 20, pp.803~807 (2008)
  16. Chen, H., "TGF-beta induced fibroblast activation protein expression, fibroblast activation protein expression increases the proliferation, adhesion, and migration of HO-8910PM", Exp. Mol. Pathol., 87, pp.187~194 (2009)
  17. Dai, L., "TWEAK promotes ovarian cancer cell metastasis via NF-kappaB pathway activation and VEGF expression", Cancer Lett., 283, pp.159~167 (2009)
  18. Ma, W., "In vitro biological activities of transmembrane superantigen staphylococcal enterotoxin A fusion protein", Cancer Immunol. Immunother., 53, pp.118~124 (2004)
  19. Sun, H., "Cytotoxic activity and constituents of the volatile oil from the roots of Patrinia scabra Bunge", Chem. Biodivers., 2, pp.1351~1357 (2005)
  20. Zhang, Y. B., "A new cytotoxic, apoptosis-inducing triterpenoid from the rhizomes of Astilbe chinensis", Chem. Biodivers., 5, pp.189~196 (2008)
  21. Sahai, E., "Mechanisms of cancer cell invasion", Curr. Opin. Genet. Dev., 15, pp.87~96 (2005)
  22. Kemler, R., "From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion", Trends Genet., 9, pp.317~321 (1993)
  23. Shapiro, L., "Structural basis of cell-cell adhesion by cadherins", Nature, 374, pp.327~337 (1995)
  24. Benest, A. V., "Cancer: blood vessels kept quiet", Nature, 458, pp.41~42 (2009)
  25. Crawford, Y., "VEGF inhibition: insights from preclinical and clinical studies", Cell Tissue. Res., 335, pp.261~269 (2009)
  26. Jain, R. K., "A new target for tumor therapy", N. Engl. J. Med., 360, pp.2669~2671 (2009)
  27. Gutierrez, L. S., "Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1", Cancer Res., 60, pp.5839~5847 (2000)
  28. Healy, A. M., "Induction of plasminogen activator inhibitor-1 in HepG2 human hepatoma cells by mediators of the acute phase response", J. Biol. Chem., 269, pp.19095~19100 (1994)
  29. Illemann, M., "Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases", Int. J. Cancer, 124, pp.1860~1870 (2009)
  30. Van den Eynden, G. G., "Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases", Int. J. Cancer, 125, pp.1494~1496 (2009)

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