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

Kimbung, Siker LU ; Lettiero, Barbara LU ; Feldt, Maria LU ; Bosch Campos, Ana LU and Borgquist, Signe LU (2016) In Oncotarget 7(37). p.59640-59651
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Cholesterol biosynthesis, Predictive biomarker, Prognosis, Statin
in
Oncotarget
volume
7
issue
37
pages
12 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:84991325613
  • wos:000387153900069
ISSN
1949-2553
DOI
10.18632/oncotarget.10746
language
English
LU publication?
yes
id
5fabbba4-235d-4718-90c7-6f62da1d8d95
date added to LUP
2016-11-08 12:09:55
date last changed
2017-10-08 04:54:21
@article{5fabbba4-235d-4718-90c7-6f62da1d8d95,
  abstract     = {<p>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.</p>},
  author       = {Kimbung, Siker and Lettiero, Barbara and Feldt, Maria and Bosch Campos, Ana and Borgquist, Signe},
  issn         = {1949-2553},
  keyword      = {Breast cancer,Cholesterol biosynthesis,Predictive biomarker,Prognosis,Statin},
  language     = {eng},
  number       = {37},
  pages        = {59640--59651},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {High expression of cholesterol biosynthesis genes is associated with resistance to statin treatment and inferior survival in breast cancer},
  url          = {http://dx.doi.org/10.18632/oncotarget.10746},
  volume       = {7},
  year         = {2016},
}