Abstract for Endocrine Society of Australia annual meeting.

Saturday, June 19, 2010

Expression and cellular activation of peroxisome proliferator-activated receptor γ in granulosa cell tumours.


Simon Chu, Chee Yong Chuan, Maria Alexiadis and Peter J Fuller
Prince Henry's Institute

Granulosa cell tumours (GCT) of the ovary are rare, hormonally-active neoplasms characterised by endocrine manifestations, an indolent course, and late relapse. Chemotherapy and hormonal therapy have proved to be of limited efficacy. Nuclear receptors (NR) are well defined targets which have a central pathogenic role in endocrine malignancy. They are potential targets for therapeutic intervention. NR have established roles in granulosa cell biology but their roles in GCT remain largely unexplored. In order to more systematically examine the NR family in GCT, we used ABI Low Density Array microfluidic cards to analyse 14 GCT and two GCT-derived cell lines for expression of the 48 NR. The levels of expression were remarkably consistent across the GCT. We found that peroxisome proliferator-activated receptor gamma (PPARg) had greater than 10 fold absolute expression when compared with either the NCBI tumour or brain reference RNA pools. PPARg agonists are regarded as potential therapeutics in the treatment of inflammatory diseases and certain cancers. Given the high expression levels of PPARg in GCT, we investigated whether the use of PPARg and/or retinoid X receptor (RXR) agonists or antagonists have an effect on GCT-derived cell lines. We observed that the PPARg/RXR agonists and antagonists had no affect on cell proliferation, cell viability or apoptosis. Although the use of PPARg agonists is unlikely to be of use in treating GCT, a combination of therapies involving knockdown of NF-kB signalling may be of benefit. We have previously observed that several other members of the steroid receptor family are transrepressed due to constitutive activation of the NF-kB signalling pathway. We are currently investigating whether PPARg is transcriptionally active in these cells using a reporter construct specific for PPARg and whether the non-responsivness to PPARg agonists or antagonists in vitro is due to NF-kB transrepression.

3 comments:

曉薇 said...

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許紀廷 said...

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韋以韋以 said...

生存乃是不斷地在內心與靈魂交戰;寫作是坐著審判自己。......................................................................