Oncotarget

Research Papers:

High expression of cholesterol biosynthesis genes is associated with resistance to statin treatment and inferior survival in breast cancer

Siker Kimbung _, Barbara Lettiero, Maria Feldt, Ana Bosch and Signe Borgquist

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

Oncotarget. 2016; 7:59640-59651. https://doi.org/10.18632/oncotarget.10746

Metrics: HTML 1034 views  |   ?  


Abstract

Siker Kimbung1, Barbara Lettiero1, Maria Feldt1, Ana Bosch1,2, Signe Borgquist1,2

1Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden

2Department of Oncology, Skåne University Hospital, Lund, Sweden

Correspondence to:

Siker Kimbung, email: Siker.kimbung@med.lu.se

Signe Borgquist, email: Signe.borgquist@med.lu.se

Keywords: statin, breast cancer, cholesterol biosynthesis, predictive biomarker, prognosis

Received: April 12, 2016    Accepted: July 10, 2016    Published: July 21, 2016

ABSTRACT

There is sufficient evidence that statins have a protective role against breast cancer proliferation and recurrence, but treatment predictive biomarkers are lacking. Breast cancer cell lines displaying diverse sensitivity to atorvastatin were subjected to global transcriptional profiling and genes significantly altered by statin treatment were identified. Atorvastatin treatment strongly inhibited proliferation in estrogen receptor (ER) negative cell lines and a commensurate response was also evident on the genome-wide transcriptional scale, with ER negative cells displaying a robust deregulation of genes involved in the regulation of cell cycle progression and apoptosis. Interestingly, atorvastatin upregulated genes involved in the cholesterol biosynthesis pathway in all cell lines, irrespective of sensitivity to statin treatment. However, the level of pathway induction; measured as the fold change in transcript levels, was inversely correlated to the effect of statin treatment on cell growth. High expression of cholesterol biosynthesis genes before treatment was associated with resistance to statin therapy in cell lines and clinical biopsies. Furthermore, high expression of cholesterol biosynthesis genes was independently prognostic for a shorter recurrence-free and overall survival, especially among ER positive tumors. Dysregulation of cholesterol biosynthesis is therefore predictive for both sensitivity to anti-cancer statin therapy and prognosis following primary breast cancer diagnosis.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 10746