Journal Article


W M Gallagher
K Jirström
J P Crown
R C Millikan
R Bernards
M J Kuhar
S M Hewitt
L Ryden
G Landberg
M J Duffy
and 9 others



middle aged antineoplastic agents hormonal prognosis apoptosis drug effects cohort studies cocaine and amphetamine regulated transcript protein breast neoplasms map kinase signaling system aged 80 and over estrogen receptor alpha human adult estrogen receptor alpha metabolism humans female therapeutic use nerve tissue proteins tamoxifen pathology cell line tumor drug therapy aged transcription genetic image processing computer assisted

The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ERα, and is an independent prognostic factor in node-negative breast cancer. (2011)

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 ERα 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.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

W M Gallagher, K Jirström, J P Crown, R C Millikan, R Bernards, M J Kuhar, S M Hewitt, L Ryden, G Landberg, M J Duffy and 9 others

Experts in our system

William M Gallagher
University College Dublin
Total Publications: 148
John Crown
Dublin City University
Total Publications: 104
Michael J Duffy
University College Dublin