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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Article

Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors

  • Authors:
    • Sarah Miller
    • Nobel Bhasin
    • Heather Urrego
    • Krzysztof Moroz
    • Brian G. Rowan
    • Meera S. Ramayya
    • Nick M. Makridakis
  • View Affiliations / Copyright

    Affiliations: The Ohio Department of Health, Columbus, OH 43215, USA, Department of Epidemiology and Tulane Cancer Center, Tulane University, New Orleans, LA 70112, USA, Department of Pathology, Tulane University School of Medicine, New Orleans, LA 70112, USA, Department of Structural and Cellular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA, Department of Pediatrics, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA
  • Pages: 627-634
    |
    Published online on: December 28, 2012
       https://doi.org/10.3892/ijo.2012.1758
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Abstract

Steroidogenic factor-1 (SF‑1), the product of the NR5A1 gene, is an essential transcription factor that is known to regulate steroidogenesis in ovarian epithelia, including the synthesis of progesterone, a suppressor of ovarian cancer. Expression of the SF‑1 protein, a potential ovarian tumor suppressor, has been demonstrated in normal OSE cells, but is lost in most ovarian tumors and ovarian tumor cell lines. We examined loss of heterozygosity (LOH) and promoter methylation as potential mechanisms that may explain the loss of SF‑1 protein in ovarian tumor tissues. Genotyping of three NR5A1 SNPs in matched tumor/normal tissues identified LOH in 16/36 (44%) of the ovarian tumors successfully analyzed, and somatic mutations (gain of allele) in 10% of the tumors. Furthermore, a methylation-sensitive restriction enzyme method was used to demonstrate statistically significant (p<0.0001) increase in the frequency of NR5A1 gene methylation in ovarian tumors (36/46; 78%) versus normal ovaries (1/11; 9%). These data suggest that the SF‑1 encoding gene exhibits frequent genetic (LOH/base substitution) and epigenetic (methylation) somatic alterations in ovarian tumors. These data also present novel molecular mechanisms that may explain the loss of SF‑1 protein in ovarian tumors, and its potential role in ovarian carcinogenesis.
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Copy and paste a formatted citation
Spandidos Publications style
Miller S, Bhasin N, Urrego H, Moroz K, Rowan BG, Ramayya MS and Makridakis NM: Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors. Int J Oncol 42: 627-634, 2013.
APA
Miller, S., Bhasin, N., Urrego, H., Moroz, K., Rowan, B.G., Ramayya, M.S., & Makridakis, N.M. (2013). Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors. International Journal of Oncology, 42, 627-634. https://doi.org/10.3892/ijo.2012.1758
MLA
Miller, S., Bhasin, N., Urrego, H., Moroz, K., Rowan, B. G., Ramayya, M. S., Makridakis, N. M."Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors". International Journal of Oncology 42.2 (2013): 627-634.
Chicago
Miller, S., Bhasin, N., Urrego, H., Moroz, K., Rowan, B. G., Ramayya, M. S., Makridakis, N. M."Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors". International Journal of Oncology 42, no. 2 (2013): 627-634. https://doi.org/10.3892/ijo.2012.1758
Copy and paste a formatted citation
x
Spandidos Publications style
Miller S, Bhasin N, Urrego H, Moroz K, Rowan BG, Ramayya MS and Makridakis NM: Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors. Int J Oncol 42: 627-634, 2013.
APA
Miller, S., Bhasin, N., Urrego, H., Moroz, K., Rowan, B.G., Ramayya, M.S., & Makridakis, N.M. (2013). Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors. International Journal of Oncology, 42, 627-634. https://doi.org/10.3892/ijo.2012.1758
MLA
Miller, S., Bhasin, N., Urrego, H., Moroz, K., Rowan, B. G., Ramayya, M. S., Makridakis, N. M."Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors". International Journal of Oncology 42.2 (2013): 627-634.
Chicago
Miller, S., Bhasin, N., Urrego, H., Moroz, K., Rowan, B. G., Ramayya, M. S., Makridakis, N. M."Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors". International Journal of Oncology 42, no. 2 (2013): 627-634. https://doi.org/10.3892/ijo.2012.1758
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