Research resource: nuclear receptors as transcriptome: discriminant and prognostic value in breast cancer

Muscat, George E. O., Eriksson, Natalie A., Byth, Karen, Loi, Sherene, Graham, Dinny, Jindal, Shalini, Davis, Melissa J., Clyne, Colin, Funder, John W., Simpson, Evan R., Ragan, Mark A., Kuczek, Elizabeth, Fuller, Peter J., Tilley, Wayne D., Leedman, Peter J. and Clarke, Christine L. (2013) Research resource: nuclear receptors as transcriptome: discriminant and prognostic value in breast cancer. Molecular Endocrinology, 27 2: 350-365. doi:10.1210/me.2012-1265

Author Muscat, George E. O.
Eriksson, Natalie A.
Byth, Karen
Loi, Sherene
Graham, Dinny
Jindal, Shalini
Davis, Melissa J.
Clyne, Colin
Funder, John W.
Simpson, Evan R.
Ragan, Mark A.
Kuczek, Elizabeth
Fuller, Peter J.
Tilley, Wayne D.
Leedman, Peter J.
Clarke, Christine L.
Title Research resource: nuclear receptors as transcriptome: discriminant and prognostic value in breast cancer
Journal name Molecular Endocrinology   Check publisher's open access policy
ISSN 0888-8809
Publication date 2013-02-01
Sub-type Article (original research)
DOI 10.1210/me.2012-1265
Volume 27
Issue 2
Start page 350
End page 365
Total pages 16
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Language eng
Formatted abstract
To identify biologically relevant groupings or clusters of nuclear receptors (NR) that are associated with breast neoplasia, with potentially diagnostic, discriminant or prognostic value, we quantitated mRNA expression levels of all 48 members of the human NR superfamily by TaqMan low-density array analysis in 116 curated breast tissue samples, including pre- and postmenopausal normal breast and both ERα+ and ERα- tumor tissue. In addition, we have determined NR levels in independent cohorts of tamoxifen-treated ERα+ and ERα- tissue samples. There were differences in relative NR mRNA expression between neoplastic and normal breast, and between ER+ and ER- tumors. First, there is overexpression of the NUR77 subgroup and EAR2 in neoplastic breast. Second, we identify a signature of five NR (ERα, EAR2, NUR77, TRα, and RARγ) that classifies breast samples with more than 97% cross-validated accuracy into normal or cancer classes. Third, we find a novel negative association between five NR (TRβ, NUR77, RORγ, COUP-TFII, and LRH1) and histological grade. Finally, four NR (COUP-TFII, TRβ, PPARγ, and MR) are significant predictors of metastasis-free survival in tamoxifen-treated breast cancers, independent of ER expression. The present study highlights the discriminant and prognostic value of NR in breast cancer; identifies novel, clinically relevant, NR signatures; and highlights NR signaling pathways with potential roles in breast cancer pathophysiology and as new therapeutic targets.
Keyword Breast neoplasia
mRNA expression
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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