Advanced

The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ER alpha, and is an independent prognostic factor in node-negative breast cancer

Brennan, D. J.; O'Connor, D. P.; Laursen, H.; McGee, S. F.; McCarthy, S.; Zagozdzon, R.; Rexhepaj, E.; Culhane, A. C.; Martin, F. M. and Duffy, M. J., et al. (2012) In Oncogene 31(30). p.3483-3494
Abstract
Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n = 690; P... (More)
Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n = 690; P = 0.002, 0.013). We also show that CART increases the transcriptional activity of ER alpha in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy. Oncogene (2012) 31, 3483-3494; doi:10.1038/onc.2011.519; published online 5 December 2011 (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cocaine- and amphetamine-regulated transcript, breast cancer, prognosis, estrogen receptor
in
Oncogene
volume
31
issue
30
pages
3483 - 3494
publisher
Nature Publishing Group
external identifiers
  • wos:000306844100001
  • scopus:84864344518
ISSN
1476-5594
DOI
10.1038/onc.2011.519
language
English
LU publication?
yes
id
be2fb0ea-6062-4228-afb6-3912a6c5e729 (old id 3070000)
date added to LUP
2012-10-05 07:05:01
date last changed
2017-07-23 03:16:40
@article{be2fb0ea-6062-4228-afb6-3912a6c5e729,
  abstract     = {Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n = 690; P = 0.002, 0.013). We also show that CART increases the transcriptional activity of ER alpha in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy. Oncogene (2012) 31, 3483-3494; doi:10.1038/onc.2011.519; published online 5 December 2011},
  author       = {Brennan, D. J. and O'Connor, D. P. and Laursen, H. and McGee, S. F. and McCarthy, S. and Zagozdzon, R. and Rexhepaj, E. and Culhane, A. C. and Martin, F. M. and Duffy, M. J. and Landberg, Göran and Rydén, Lisa and Hewitt, S. M. and Kuhar, M. J. and Bernards, R. and Millikan, R. C. and Crown, J. P. and Jirström, Karin and Gallagher, W. M.},
  issn         = {1476-5594},
  keyword      = {cocaine- and amphetamine-regulated transcript,breast cancer,prognosis,estrogen receptor},
  language     = {eng},
  number       = {30},
  pages        = {3483--3494},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ER alpha, and is an independent prognostic factor in node-negative breast cancer},
  url          = {http://dx.doi.org/10.1038/onc.2011.519},
  volume       = {31},
  year         = {2012},
}