Interactions between prostaglandin E(2), liver receptor homologue-1, and aromatase in breast cancer.
Local synthesis of estrogens within breast adipose tissue by cytochrome P450 aromatase contributes to the growth of postmenopausal breast cancers. One of the major stimulators of aromatase expression in breast is prostaglandin E(2) (PGE(2)) derived from tumorous epithelium and/or infiltrating macrophages. Recently, the orphan nuclear receptor, liver receptor homologue-1 (LRH-1), has also been shown to regulate aromatase expression in breast adipose tissue. We therefore examined the expression of, and correlations between, aromatase and LRH-1 mRNA in a panel of breast carcinoma tissues and adjacent adipose tissue. LRH-1 mRNA expression was low in normal breast tissue but markedly elevated in both breast carcinoma tissue and adipose tissue surrounding the tumor invasion (thereby paralleling aromatase expression). Laser capture microdissection localized the site of LRH-1 expression to tumor epithelial cells but not to intratumoral stromal cells. A strong correlation between LRH-1 and aromatase mRNA levels was observed in tumor-containing adipose tissue but not in tumor tissue. Ectopic expression of LRH-1 in primary human adipose stromal cells strongly activated endogenous aromatase mRNA expression and enzyme activity. Finally, treatment of adipose stromal cells with PGE(2) induced expression of both LRH-1 and aromatase. We suggest that PGE(2) derived from breast tumor tissue may increase aromatase expression in the surrounding adipose stroma in part by inducing LRH-1 in these cells. The roles of LRH-1 in breast cancer proliferation merit further study.
Zhou
Jiong
J
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Suzuki
Takashi
T
Kovacic
Agnes
A
Saito
Ryoko
R
Miki
Yasuhiro
Y
Ishida
Takanori
T
Moriya
Takuya
T
Simpson
Evan R
ER
Sasano
Hironobu
H
Clyne
Colin D
CD
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000328:Adult; D000368:Aged; D001141:Aromatase / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C082631:NR5A2 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D001141:Aromatase; D015232:Dinoprostone