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Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer

Henna Heinonen1, Anni Nieminen, Matti Saarela

  • 1Institute of Biomedicine and Biomedicum Biochip Center, Genome-Scale Biology Research Program, University of Helsinki, Finland. henna.heinonen@helsinki.fi

BMC Genomics
|July 26, 2008
PubMed
Abstract

Insights

The 70 kDa ribosomal protein S6 kinase (RPS6KB1) pathway is altered in breast cancer. This study identified novel downstream targets of this pathway, which may aid in diagnosis and treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The 70 kDa ribosomal protein S6 kinase (RPS6KB1) is overexpressed in 10-30% of breast cancers.
  • p70S6K, a kinase regulated by the PI3K/mTOR pathway, is crucial for cell cycle, growth, and survival.
  • RPS6KB1 amplification and overexpression are linked to aggressive breast cancer and poor prognosis.

Purpose of the Study:

  • To determine gene expression profiles dependent on p70S6K and the PI3K/mTOR/p70S6K pathway in breast cancer.
  • To identify novel downstream targets of the PI3K/mTOR/p70S6K pathway.

Main Methods:

  • Microarray analysis of five breast cancer cell lines with known gene copy number and expression alterations.
  • siRNA silencing of RPS6KB1 in two breast cancer cell lines.
  • Correlation of gene expression profiles with inhibition of PI3K/mTOR pathway using Ly294002 and rapamycin.

Main Results:

  • Silencing p70S6K altered 109 and 173 genes in two cell lines, with 67 genes altered in both.
  • 17 genes, including VTCN1 and CDKN2B, overlapped with genes affected by PI3K or mTOR inhibition.
  • Identified novel downstream targets of the PI3K/mTOR/p70S6K pathway.

Conclusions:

  • The identified downstream targets of p70S6K and the PI3K/mTOR/p70S6K pathway may have diagnostic value.
  • Understanding these targets can contribute to improved breast cancer patient prognosis.

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