Aberrant hypomethylation-mediated AGR2 overexpression induces an aggressive phenotype in ovarian cancer cells

  • Authors:
    • Hye Youn Sung
    • Eun Nam Choi
    • Dahyun Lyu
    • Ae Kyung Park
    • Woong Ju
    • Jung-Hyuck Ahn
  • View Affiliations

  • Published online on: June 11, 2014     https://doi.org/10.3892/or.2014.3243
  • Pages: 815-820
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Abstract

The metastatic properties of cancer cells result from genetic and epigenetic alterations that lead to the abnormal expression of key genes regulating tumor phenotypes. Recent discoveries suggest that aberrant DNA methylation provides cancer cells with advanced metastatic properties; however, the precise regulatory mechanisms controlling metastasis-associated genes and their roles in metastatic transformation are largely unknown. We injected SK-OV-3 human ovarian cancer cells into the perineum of nude mice to generate a mouse model that mimics human ovarian cancer metastasis. We analyzed the mRNA expression and DNA methylation profiles in metastasized tumor tissues in the mice. The pro-oncogenic anterior gradient 2 (AGR2) gene showed increased mRNA expression and hypomethylation at CpG sites in its promoter region in the metastatic tumor tissues compared with the cultured SK-OV-3 cells. We identified crucial cytosine residues at CpG sites in the AGR2 promoter region. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reduced the level of CpG methylation in the AGR2 promoter and increased the level of AGR2 expression. Next, we explored the functional role of AGR2 in the metastatic transformation of SK-OV-3 cells. SK-OV-3 cells overexpressing AGR2 showed increased migratory and invasive activity. Our results indicate that DNA methylation within the AGR2 promoter modulates more aggressive cancer cell phenotypes.

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August-2014
Volume 32 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Sung HY, Choi EN, Lyu D, Park AK, Ju W and Ahn J: Aberrant hypomethylation-mediated AGR2 overexpression induces an aggressive phenotype in ovarian cancer cells. Oncol Rep 32: 815-820, 2014.
APA
Sung, H.Y., Choi, E.N., Lyu, D., Park, A.K., Ju, W., & Ahn, J. (2014). Aberrant hypomethylation-mediated AGR2 overexpression induces an aggressive phenotype in ovarian cancer cells. Oncology Reports, 32, 815-820. https://doi.org/10.3892/or.2014.3243
MLA
Sung, H. Y., Choi, E. N., Lyu, D., Park, A. K., Ju, W., Ahn, J."Aberrant hypomethylation-mediated AGR2 overexpression induces an aggressive phenotype in ovarian cancer cells". Oncology Reports 32.2 (2014): 815-820.
Chicago
Sung, H. Y., Choi, E. N., Lyu, D., Park, A. K., Ju, W., Ahn, J."Aberrant hypomethylation-mediated AGR2 overexpression induces an aggressive phenotype in ovarian cancer cells". Oncology Reports 32, no. 2 (2014): 815-820. https://doi.org/10.3892/or.2014.3243