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The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study.

Publication ,  Journal Article
Alvarez Secord, A; Darcy, KM; Hutson, A; Huang, Z; Lee, PS; Jewell, EL; Havrilesky, LJ; Markman, M; Muggia, F; Murphy, SK
Published in: Gynecol Oncol
November 2011

OBJECTIVES: To elucidate the regulation of MASPIN expression in epithelial ovarian cancer (EOC) and associations with p53 status and MASPIN promoter methylation. METHODS: Seven EOC cell lines and 110 advanced stage EOC specimens were analyzed for MASPIN promoter methylation. The cell lines were treated with 5-azacytidine (5-azaC) and evaluated for MASPIN promoter methylation, protein, and mRNA expression. Wild-type (wt) p53 was transiently transfected into the mutant p53 (m p53) SKOV3 cells which were treated with 5-azaC. Phosphor imager analysis quantified the percent methylation of the MASPIN promoter. RESULTS: Of the 3 MASPIN-low m p53 cell lines 2 had greater than 5% MASPIN methylation whereas only 1 of 4 MASPIN-high wt p53 cell lines had greater than 5% MASPIN methylation. Despite the presence of aberrant MASPIN promoter methylation in SKOV3 cells, wt p53-transfection alone resulted in a 3.3-fold increase in MASPIN mRNA. The combination of 5-azaC and wt p53-transfection produced a 36% reduction in MASPIN promoter methylation and 4.5-fold increase in MASPIN transcription. Among the 110 ovarian cancer specimens analyzed for methylation of the MASPIN promoter, 81.8% were weakly methylated, 14.5% were heavily methylated and 3.6% were fully methylated. There was no relationship between promoter methylation and p53 status or MASPIN protein expression. However, MASPIN protein was 6 times more likely to be detected in cancer specimens that harbor a p53 mutation relative to cancer specimens with a wt p53 gene. CONCLUSION: The regulation of MASPIN is a complex multifactorial process that may be controlled by both p53-dependent and -independent epigenetic mechanisms.

Duke Scholars

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

November 2011

Volume

123

Issue

2

Start / End Page

314 / 319

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Serpins
  • Promoter Regions, Genetic
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms, Glandular and Epithelial
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
  • DNA Methylation
 

Citation

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MLA
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Alvarez Secord, A., Darcy, K. M., Hutson, A., Huang, Z., Lee, P. S., Jewell, E. L., … Murphy, S. K. (2011). The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study. Gynecol Oncol, 123(2), 314–319. https://doi.org/10.1016/j.ygyno.2011.08.003
Alvarez Secord, Angeles, Kathleen M. Darcy, Alan Hutson, Zhiqing Huang, Paula S. Lee, Elizabeth L. Jewell, Laura J. Havrilesky, Maurie Markman, Franco Muggia, and Susan K. Murphy. “The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study.Gynecol Oncol 123, no. 2 (November 2011): 314–19. https://doi.org/10.1016/j.ygyno.2011.08.003.
Alvarez Secord A, Darcy KM, Hutson A, Huang Z, Lee PS, Jewell EL, et al. The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study. Gynecol Oncol. 2011 Nov;123(2):314–9.
Alvarez Secord, Angeles, et al. “The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study.Gynecol Oncol, vol. 123, no. 2, Nov. 2011, pp. 314–19. Pubmed, doi:10.1016/j.ygyno.2011.08.003.
Alvarez Secord A, Darcy KM, Hutson A, Huang Z, Lee PS, Jewell EL, Havrilesky LJ, Markman M, Muggia F, Murphy SK. The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study. Gynecol Oncol. 2011 Nov;123(2):314–319.
Journal cover image

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

November 2011

Volume

123

Issue

2

Start / End Page

314 / 319

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Serpins
  • Promoter Regions, Genetic
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms, Glandular and Epithelial
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
  • DNA Methylation