Cell density is a critical determinant of aromatase expression in adipose stromal cells.
Obesity is associated with an increased risk of breast cancer among postmenopausal women. This is at least partly due to excessive estrogen production in adipose tissue of obese women. Aromatase, the key enzyme in estrogen biosynthesis, is an important target in endocrine therapy for estrogen receptor (ER)-positive postmenopausal breast cancer. In this study we show that high confluency of human adipose stromal cells (ASCs) cultured in vitro can significantly stimulate aromatase gene expression and reduce the expression of breast tumor suppressor BRCA1 and members of the NR4A orphan nuclear family. Furthermore, small interfering RNA (siRNA)-mediated knockdown of Nurr1, a member of the NR4A family, substantially increased aromatase expression. Lastly, we found that the cell density-triggered inducibility of aromatase expression varies in ASCs isolated from different disease-free individuals. Our finding highlights the impact of increased cell number on estrogen biosynthesis as in the case of excessive adiposity.
Ghosh
Sagar
S
Department of Molecular Medicine, Institute of Biotechnology, 15335 Lambda Drive, University of Texas, Health Science Center at San Antonio, San Antonio, TX 78245, USA.
Hu
Yanfen
Y
Li
Rong
R
D000273:Adipose Tissue / Q000166:cytology*; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology*
D019313:BRCA1 Protein; C539882:NR4A2 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D001141:Aromatase