The expression and correlation between the transcription factor FOXP1 and estrogen receptors in epithelial ovarian cancer

Biochimie. 2015 Feb:109:42-8. doi: 10.1016/j.biochi.2014.12.001. Epub 2014 Dec 10.

Abstract

Background: Estrogen plays an important role in the progression of ovarian cancer in humans. FOXP1 belongs to the forkhead/winged-helix transcription factor family, and previous research indicated that FOXP1 functioned as a tumor suppressor gene. FOXP1 may be similar to FOXA1 and is closely related to steroid hormone receptors, but the relationship between FOXP1 and ER currently remains unclear.

Methods: Ovarian tumors (60 malignant cases, 26 borderline cases, and 13 benign cases) and 14 normal ovarian tissues were collected retrospectively. Immunohistochemistry, western blotting and real-time PCR were used to characterize the expression patterns of FOXP1, ERα, and ERβ both at the mRNA and protein levels. We also used co-immunoprecipitation and immunofluorescent colocalization to investigate whether a correlation exists between FOXP1 and ERα/ERβ in ovarian cancer tissues.

Results: The mRNA level for FOXP1 and ERβ in ovarian carcinoma tissues decreased, while the expression level of ERα mRNA increased compared with normal ovarian tissues. With an increase in the degree of ovarian carcinoma malignancy, the ERα expression level also increased. The expression pattern of ERβ in ovarian neoplasms was similar to that of the FOXP1 protein; presenting nuclear staining decreased, while cytoplasmic expression increased. Colocalization of FOXP1, ERα, and ERβ was present in the cytoplasm, with ERβ specific co-localization with FOXP1 in the perinuclear area. While immunoprecipitates created with FOXP1 mouse anti-human monoclonal antibody showed a positive reaction to an anti-ER antibody, immunoprecipitates containing anti-ER antibody and react to anti-FOXP1 antibody.

Conclusion: Interactions between FOXP1 and ER may play a pivotal role in the progression of ovarian cancer, and the activation or induction of FOXP1 and ERβ expression in cancer cells may inhibit tumor proliferation.

Keywords: Estrogen receptor; FOXP1; Interaction; Ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carcinoma, Ovarian Epithelial
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / genetics*
  • Estrogen Receptor beta / metabolism
  • Female
  • Fluorescent Antibody Technique
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • FOXP1 protein, human
  • Forkhead Transcription Factors
  • RNA, Messenger
  • Repressor Proteins