Distinct nuclear receptor expression in stroma adjacent to breast tumors

Knower, Kevin C., Chand, Ashwini L., Eriksson, Natalie, Takagi, Kiyoshi, Miki, Yasuhiro, Sasano, Hironobu, Visvader, Jane E., Lindeman, Geoffrey J., Funder, John W., Fuller, Peter J., Simpson, Evan R., Tilley, Wayne D., Leedman, Peter J., Graham, J. Dinny, Muscat, George E. O., Clarke, Christine L. and Clyne, Colin D. (2013) Distinct nuclear receptor expression in stroma adjacent to breast tumors. Breast Cancer Research and Treatment, 142 1: 211-223. doi:10.1007/s10549-013-2716-6

Author Knower, Kevin C.
Chand, Ashwini L.
Eriksson, Natalie
Takagi, Kiyoshi
Miki, Yasuhiro
Sasano, Hironobu
Visvader, Jane E.
Lindeman, Geoffrey J.
Funder, John W.
Fuller, Peter J.
Simpson, Evan R.
Tilley, Wayne D.
Leedman, Peter J.
Graham, J. Dinny
Muscat, George E. O.
Clarke, Christine L.
Clyne, Colin D.
Title Distinct nuclear receptor expression in stroma adjacent to breast tumors
Journal name Breast Cancer Research and Treatment   Check publisher's open access policy
ISSN 0167-6806
Publication date 2013-11
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s10549-013-2716-6
Volume 142
Issue 1
Start page 211
End page 223
Total pages 13
Place of publication New York, NY United States
Publisher Springer New York LLC
Collection year 2014
Language eng
Formatted abstract
The interaction between breast tumor epithelial and stromal cells is vital for initial and recurrent tumor growth. While breast cancer-associated stromal cells provide a favorable environment for proliferation and metastasis, the molecular mechanisms contributing to this process are not fully understood. Nuclear receptors (NRs) are intracellular transcription factors that directly regulate gene expression. Little is known about the status of NRs in cancer-associated stroma. Nuclear Receptor Low-Density Taqman Arrays were used to compare the gene expression profiles of all 48 NR family members in a collection of primary cultured cancer-associated fibroblasts (CAFs) obtained from estrogen receptor (ER)α positive breast cancers (n = 9) and normal breast adipose fibroblasts (NAFs) (n = 7). Thirty-three of 48 NRs were expressed in both the groups, while 11 NRs were not detected in either. Three NRs (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1); estrogen-related receptor beta (ERR-β); and RAR-related orphan receptor beta (ROR-β)) were only detected in NAFs, while one NR (liver receptor homolog-1 (LRH-1)) was unique to CAFs. Of the NRs co-expressed, four were significantly down-regulated in CAFs compared with NAFs (RAR-related orphan receptor-α (ROR-α); Thyroid hormone receptor-β (TR-β); vitamin D receptor (VDR); and peroxisome proliferator-activated receptor-γ (PPAR-γ)). Quantitative immunohistochemistry for LRH-1, TR-β, and PPAR-γ proteins in stromal fibroblasts from an independent panel of breast cancers (ER-positive (n = 15), ER-negative (n = 15), normal (n = 14)) positively correlated with mRNA expression profiles. The differentially expressed NRs identified in tumor stroma are key mediators in aromatase regulation and subsequent estrogen production. Our findings reveal a distinct pattern of NR expression that therefore fits with a sustained and increased local estrogen microenvironment in ER-positive tumors. NRs in CAFs may provide a new avenue for the development of intratumoral-targeted therapies in breast cancer.
Keyword Nuclear receptors
Breast cancer
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
Institute for Molecular Bioscience - Publications
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