Regulation of aromatase expression by the nuclear receptor LRH-1 in adipose tissue.
Aromatase is the enzyme responsible for estrogen production, and is the product of the CYP19 gene. This gene is under the control of many tissue-specific promoters, each of which is regulated by different cohorts of factors. In normal breast adipose tissue, relatively low levels of aromatase are expressed via the action of the adipose specific promoter I.4. Breast tumor-derived factors such as prostaglandin E(2) (PGE(2)) strongly stimulate aromatase expression via an alternative promoter, promoter II, leading to increased estrogenic drive and tumor growth. Understanding the mechanisms that regulate promoter II activity in tumorous breast may therefore identify new targets for breast cancer drug discovery. The current study describes the role of the orphan nuclear receptor LRH-1 and its co-regulators in modulating aromatase expression in breast adipose tissue.
Clyne
Colin D
CD
Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Vic. 3168, Australia. colin.clyne@med.monash.edu.au
Kovacic
Agnes
A
Speed
Caroline J
CJ
Zhou
Jiong
J
Pezzi
Vincenzo
V
Simpson
Evan R
ER
D000273:Adipose Tissue; D000818:Animals; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*
C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D001141:Aromatase