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The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis

Katie Lin1, Stavroula Baritaki2, Silvia Vivarelli3,4

  • 1Jonsson Comprehensive Cancer Center, Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

Antioxidants (Basel, Switzerland)
|June 24, 2022
PubMed

Insights

Inducible nitric oxide synthase (iNOS) interacts with breast cancer genes like HER2 and BRCA1/2. Understanding this crosstalk may reveal new therapeutic targets for aggressive breast cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production have dual roles in cancer, influencing tumor growth and suppression.
  • Overexpressed iNOS in human breast cancer is linked to pro-tumorigenic activity and poor prognosis.
  • Oncogenes HER2, BRCA1, and BRCA2 are associated with malignancy, but their relationship with iNOS is unclear.

Purpose of the Study:

  • To explore the potential cross-talk signaling pathways between breast cancer proto-oncogenes and the iNOS axis.
  • To investigate the interrelationship between iNOS expression and the regulation of proto-oncogenes (HER2, BRCA1/2) in breast cancer.
  • To discuss the role of iNOS, HER2, BRCA1/2, and NO metabolism in cancer stem cell pathophysiology.

Main Methods:

  • Literature review on molecular regulation of proto-oncogenes and iNOS in breast cancer.
  • Discussion of iNOS, HER2, BRCA1/2, and NO metabolism in cancer stem cells.
  • Bioinformatic analysis to identify molecular alterations associated with breast cancer aggressiveness.

Main Results:

  • Bioinformatic analyses suggest associations between BRCA1/2 mutations, HER2 amplifications, and dysregulation of the nitric oxide synthase (NOS) pathway.
  • Evidence points to potential molecular alterations driving breast cancer aggressiveness through NOS pathway disruption.
  • The interrelationship between iNOS and key breast cancer oncogenes warrants further investigation.

Conclusions:

  • The cross-talk between breast cancer proto-oncogenes and the iNOS pathway is a critical area for future research.
  • Identifying regulatory mechanisms of iNOS and oncogene expression could lead to novel therapeutic targets.
  • Targeting these pathways may offer new treatment strategies for refractory breast cancers.
Keywords:
BRCA1BRCA2HER2TNBCbreast canceriNOS/NOS2nitric oxide

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