PIK3CA is implicated as an oncogene in ovarian cancer

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Published on: January 12, 2020

L Shayesteh1, Y Lu, W L Kuo

  • 1UCSF Cancer Center, University of California, San Francisco 941430-0808, USA.

Nature Genetics
|January 23, 1999
PubMed

Insights

The PIK3CA gene, often amplified in ovarian cancers, drives tumor growth by increasing phosphatidylinositol 3-kinase (PI3-kinase) activity. Inhibiting this pathway slows cancer cell proliferation and promotes apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ovarian cancer is a leading cause of cancer death with poorly understood molecular drivers.
  • Comparative genomic hybridization (CGH) studies identify DNA copy number alterations in cancer development.
  • The 3q26 region, amplified in ~40% of ovarian cancers, harbors the PIK3CA gene.

Purpose of the Study:

  • To investigate the role of PIK3CA in ovarian cancer.
  • To determine if increased PIK3CA copy number correlates with gene expression, protein levels, and enzyme activity.
  • To assess the therapeutic potential of PI3-kinase inhibition in ovarian cancer models.

Main Methods:

  • Comparative genomic hybridization (CGH) to assess PIK3CA copy number.
  • Quantitative PCR and Western blotting to measure PIK3CA transcription and p110alpha protein expression.
  • Enzyme assays to determine PI3-kinase activity.
  • In vitro treatment with PI3-kinase inhibitor LY294002.

Main Results:

  • PIK3CA copy number is frequently increased in ovarian cancers.
  • Increased PIK3CA copy number correlates with elevated PIK3CA transcription, p110alpha protein expression, and PI3-kinase activity.
  • Inhibition of PI3-kinase with LY294002 reduced ovarian cancer cell proliferation and induced apoptosis.

Conclusions:

  • PIK3CA is frequently amplified and activated in ovarian cancer.
  • PIK3CA acts as an oncogene, playing a significant role in ovarian cancer progression.
  • Targeting the PI3-kinase pathway represents a potential therapeutic strategy for ovarian cancer.

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