The orphan nuclear receptor LRH-1 and ERα activate GREB1 expression to induce breast cancer cell proliferation.

Background: Liver Receptor Homolog 1 (LRH-1, NR5A2) is an orphan nuclear receptor that is over-expressed in cancers in tissues such as the breast, colon and pancreas. LRH-1 plays important roles in embryonic development, steroidogenesis and cholesterol homeostasis. In tumor cells, LRH-1 induces proliferation and cell cycle progression.

Tissue-specific regulation of aromatase promoter II by the orphan nuclear receptor LRH-1 in breast adipose stromal fibroblasts.

In postmenopausal breast cancers, the increase in aromatase expression observed in tumour associated adipose stromal cells is mediated via the upregulation of promoter II (PII) transcription. Factors such as PGE₂ which are secreted from breast carcinomas induce PII expression. The orphan nuclear receptor LRH-1/NR5A2 is one of the critical downstream transcriptional mediators of this effect.