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Published on: October 27, 2020

Ets-2 and p160 proteins collaborate to regulate c-Myc in endocrine resistant breast cancer

D Al-azawi1, M Mc Ilroy, G Kelly

  • 1Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland.

Oncogene
|December 7, 2007
PubMed

Insights

Epidermal Growth Factor (EGF) signaling activates Ets-2, which, with p160 coactivators SRC-1 and SRC-3, drives the oncogene myc. This pathway is linked to endocrine-resistant breast cancer and reduced survival.

Area of Science:

  • Molecular Oncology
  • Endocrinology
  • Cell Signaling

Background:

  • p160 coactivator proteins are associated with endocrine resistance in breast cancer.
  • p160 proteins primarily interact with steroid receptors but also with non-nuclear transcription factors like Ets proteins.

Purpose of the Study:

  • To investigate the role of p160 coactivators and Ets proteins in endocrine-resistant breast cancer.
  • To elucidate the molecular mechanisms linking growth factor signaling to oncogene regulation in treatment-resistant breast cancer.

Main Methods:

  • Analysis of Ets-2 and Ets-1 transcriptional regulation of the oncogene myc in endocrine-resistant breast cancer cells.
  • Investigation of the dependency of Ets-2/myc regulation on p160 proteins SRC-1 and SRC-3.
  • Correlation analysis of Ets-2, SRC-1, SRC-3, and c-Myc expression with clinical data in breast cancer patients.

Main Results:

  • Epidermal Growth Factor (EGF) induced Ets-2, not Ets-1, to transcriptionally regulate myc in resistant breast cancer cells.
  • Ets-2 regulation of myc was dependent on SRC-1 and SRC-3 coactivators.
  • High expression of Ets-2, SRC-1, and c-Myc correlated with reduced disease-free survival in patients with locally advanced breast cancer.

Conclusions:

  • SRC-1 utilizes the MAP kinase effector transcription factor Ets-2 to regulate oncogene myc production.
  • These signaling pathways involving Ets-2, SRC-1, and myc may contribute to the development of steroid-resistant or independent breast cancer.
  • Ets-2 and SRC-1 are potential prognostic markers for breast cancer patients.

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