Role of Cyclin E as an Early Event in Ovarian Carcinogenesis

Abstract

Cyclin E amplification and overexpression characterizes a subset of epithelial ovarian cancers. We hypothesized that this subset of tumors may demonstrate an enhanced response to targeted therapy with the proteasome inhibitor, bortezomib. Cyclin E also exists in multiple low molecular weight (LMW) isoforms in cancer cells which demonstrate greater neoplastic activity. A natural dietary phytochemical called Indole-3-Carbinol (I3C) disrupts cyclin E processing through the inhibition of the enzyme that cleaves cyclin E into its LMW isoforms. When combining I3C with bortezomib, we found I3C to synergistically sensitize ovarian cancer cells to bortezomib. This finding has translational potential as bortezomib as a singleagent was found to have minimal activity in a phase II treatment trial of recurrent ovarian cancer. This finding could re-introduce bortezomib to the therapeutic armamentarium against ovarian cancer if the in vitro results replicate in mice and humans.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2010
Accession Number
ADA533483

Entities

People

  • Christine Walsh

Organizations

  • Cedars-Sinai Medical Center

Tags

DTIC Thesaurus Topics

  • Amplification
  • Antineoplastic Agents
  • Cancer
  • Carbinols
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chromosomes
  • Gene Expression
  • Gynecologic Cancers
  • Inhibition
  • Inhibitors
  • Molecular Weight
  • Neoplasms
  • Ovarian Cancer
  • Phytochemicals
  • Proteins

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Oncology (Cancer Research).