Altered mammary gland morphogenesis in Liver Receptor Homolog-1 transgenic mouse

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 338-365-Metabolic & Stress Receptors in Energy Homeostasis
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-345
Kyren Aloysious Lazarus*1, Colin D Clyne2 and Ashwini L Chand2
1Prince Henry's Institute, Clayton, Australia, 2Prince Henry's Institute, Clayton VIC, Australia
Liver Receptor Homologue-1 (LRH-1) is expressed in approximately 40% of invasive breast cancers. It has roles in driving E2-dependent tumour growth via (i) regulation of aromatase, the enzyme responsible for E2 biosynthesis, and (ii) increasing tumour cell proliferation, migration and invasion. The role of LRH-1 in normal mouse mammary development and breast cancer in-vivo is unknown. To explore this, we have generated a doxycycline (dox)-inducible mammary specific LRH-1 knock-in mouse in which the MMTV promoter induces the reverse tetracycline transactivator, thereby allowing for selective expression of the human LRH-1 transgene specifically in breast epithelial cells.

We show (i) qPCR revealed no human transgene expression in any tissue of untreated animals. However, LRH-1 transcript and protein expression was observed in mammary epithelial cells of dox-treated animals following both short- (three weeks) and long- (three months) term dox treatment. To further our findings, (ii) we demonstrated an increase in Ki-67 immunoreactivity in luminal epithelial cells of dox treated animals, suggesting that LRH-1 induces mammary epithelial cell proliferation in vivo, as it does in vitro.

Finally, (iii) altered mammary gland morphogenesis was observed in dox-treated animals as demonstrated by a reduction in lateral bud number at both 3 week and 3 month time points. This prompted us to investigate the expression levels of transforming growth factor (TGF-β); a known factor that inhibits mammary gland morphogenesis. We revealed an induction of TGF-β immunoreactivity and transcript levels in dox-treated animals. We conclude that the effects of LRH-1 on ductal morphogenesis and branching are likely mediated via activation of TGFβ.

This study characterises a novel LRH-1 transgenic mouse which enables further exploration into the roles of LRH-1 in mammary development and provides a valuable model to further develop LRH-1 antagonist’s in-vivo.

Nothing to Disclose: KAL, CDC, ALC

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: United States Department of Defense; Victorian Cancer Agency; Swinburne University Postgraduate Research Award