Antitumor effect of E1A in ovarian cancer by cytoplasmic sequestration of activated ERK by PEA15

C. Bartholomeusz, H. Itamochi, M. Nitta, Hideyuki Saya, M. H. Ginsberg, N. T. Ueno

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The adenovirus type 5 gene E1A is known to suppress tumorigenicity by transcriptionally downregulating HER-2/neu (HER2) or by inducing apoptosis. We show here that E1A also suppressed the tumorigenicity of the low-HER2-expressing ovarian cancer cell line OVCAR-3 by decreasing cell proliferation. We further found that the mechanism responsible for this reduced proliferation is the presence of PEA15 (phosphoprotein enriched in astrocytes), which is upregulated by E1A in ovarian cancer; PEA15 promotes translocation of ERK from the nucleus to the cytoplasm, leading to inhibition of ERK-dependent transcription and proliferation. Indeed, siRNA-mediated knockdown of PEA15 expression in OVCAR-3 stable E1A transfectants resulted in a nuclear accumulation of the active form of ERK, followed by an increase in Elk-1 activity, DNA synthesis, and anchorage-independent growth. Finally, PEA15 by itself suppressed colony formation in breast and ovarian cancer cell lines, in which E1A is known to have antitumor activity. We conclude that part of the antitumor effect of E1A in ovarian cancer results from cytoplasmic sequestration of the activated form of ERK by PEA15.

Original languageEnglish
Pages (from-to)79-90
Number of pages12
JournalOncogene
Volume25
Issue number1
DOIs
Publication statusPublished - 2006 Jan 5
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Cell Line
Phosphoproteins
Adenoviridae
Astrocytes
Small Interfering RNA
Cytoplasm
Down-Regulation
Cell Proliferation
Apoptosis
Breast Neoplasms
DNA
Growth
Genes

Keywords

  • Adenovirus type 5 E1A
  • ERK
  • Ovarian neoplasms
  • PEA15
  • Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Antitumor effect of E1A in ovarian cancer by cytoplasmic sequestration of activated ERK by PEA15. / Bartholomeusz, C.; Itamochi, H.; Nitta, M.; Saya, Hideyuki; Ginsberg, M. H.; Ueno, N. T.

In: Oncogene, Vol. 25, No. 1, 05.01.2006, p. 79-90.

Research output: Contribution to journalArticle

Bartholomeusz, C, Itamochi, H, Nitta, M, Saya, H, Ginsberg, MH & Ueno, NT 2006, 'Antitumor effect of E1A in ovarian cancer by cytoplasmic sequestration of activated ERK by PEA15', Oncogene, vol. 25, no. 1, pp. 79-90. https://doi.org/10.1038/sj.onc.1209014
Bartholomeusz, C. ; Itamochi, H. ; Nitta, M. ; Saya, Hideyuki ; Ginsberg, M. H. ; Ueno, N. T. / Antitumor effect of E1A in ovarian cancer by cytoplasmic sequestration of activated ERK by PEA15. In: Oncogene. 2006 ; Vol. 25, No. 1. pp. 79-90.
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