Direct inhibition of eIF4E reduced cell growth in endometrial adenocarcinoma

J Cancer Res Clin Oncol. 2011 Mar;137(3):463-9. doi: 10.1007/s00432-010-0902-z. Epub 2010 May 13.

Abstract

Purpose: Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in many cancer and is emerging as a potential therapeutic target. Yet data on the expression of eIF4E in endometrial cancer are lacking.

Methods: Immunohistochemistry was used to evaluate the expression of eIF4E in 62 endometrial cancer surgical specimens. We subsequently evaluated whether inhibition of eIF4E by siRNA would have an impact on cell growth in endometrial cancer cell lines, using the MTT cell proliferation assay.

Results: According to a chosen cutoff value, 36 (58.1%) of 62 patient specimens scored as eIF4E positive. The positivity of eIF4E was significantly more frequent in tumors extending outside the uterus (stage III/IV vs. stage I/II, P = 0.027). Lastly, downregulation of eIF4E by siRNA reduced the growth of HEC-1A cells significantly but had a somewhat weaker effect in Ishikawa cells (P < 0.001).

Conclusions: Expressions of eIF4E correlated with prognosis of endometrial adenocarcinomas. Our results suggest that eIF4E might be a promising therapeutic target in endometrial cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / metabolism
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Endometrioid / therapy*
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Disease-Free Survival
  • Down-Regulation
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / therapy*
  • Eukaryotic Initiation Factor-4E / antagonists & inhibitors*
  • Eukaryotic Initiation Factor-4E / biosynthesis
  • Eukaryotic Initiation Factor-4E / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Transfection

Substances

  • Eukaryotic Initiation Factor-4E
  • RNA, Small Interfering