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Global Transcriptional Changes Following Statin Treatment in Breast Cancer

Olöf Bjarnadottir1, Siker Kimbung2, Ida Johansson2

  • 1Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden. Department of Oncology, Skåne University Hospital, Lund, Sweden.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|April 5, 2015
PubMed
Abstract

Insights

Statins like atorvastatin may impact breast cancer by altering gene expression, potentially inhibiting the MAPK pathway and promoting apoptosis. Further research is needed to fully understand these antitumoral mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Statins are known to have potential antitumoral effects.
  • The precise mechanisms behind statin-induced anticancer activity remain unclear.
  • This study investigates statin effects on gene expression in breast cancer.

Purpose of the Study:

  • To explore statin-induced changes in global gene expression profiles in primary breast cancer.
  • To elucidate the molecular mechanisms underlying the antitumoral effects of statins.
  • To identify specific genes and pathways affected by atorvastatin treatment.

Main Methods:

  • A window-of-opportunity phase II clinical trial using atorvastatin (80 mg/day) for 2 weeks presurgically in 50 breast cancer patients.
  • Analysis of pre- and posttreatment tumor samples using Significance Analysis of Microarrays (SAM) to identify differentially expressed genes.
  • Gene expression analysis in atorvastatin-treated breast cancer cell lines (MCF7, BT474, SKBR3, MDAMB231) using SAM, gene ontology, Systematic Motif Analysis Retrieval Tool (SMART), Literature Vector Analysis (LitVAn), and GeneGo Pathways Software.

Main Results:

  • Comparative analysis revealed 407 significantly differentially expressed genes in clinical samples (32 upregulated, 375 downregulated).
  • Atorvastatin treatment led to significant upregulation of genes including DUSP1, RHOB1, GADD45B, and RGS1.
  • Gene ontology, LitVAn, and SMART analyses indicated statin-induced effects on apoptotic and MAPK pathways, with cell line studies showing upregulation of mevalonate and proapoptotic pathways.

Conclusions:

  • Atorvastatin treatment induces significant changes in global tumor gene expression profiles.
  • Evidence suggests statin-induced inhibition of the MAPK pathway.
  • Proapoptotic events are implicated as a key mechanism in statin's potential anticancer effects.

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