C90
Activation of PPARγ induces PTEN expression in endometrial cancer cell lines
Mahshid Nickkho-Amiry, Cathrine Holland, Mildred Cretney
Academic unit of Obstetrics and Gynaecology, University of Manchester, School of Cancer and Imaging Sciences, Saint Mary's Hospital, Manchester, UK
Background
The PPAR family of nuclear transcription factors is increasingly implicated in the development of a number of solid tumours. In healthy individuals PPARγ is involved in adipocyte differentiation and glucose homeostasis. Both obesity and diabetes mellitus are risk factors for endometrioid endometrial cancer. Mutation of the tumour suppressor PTEN is an early event in the development of this cancer although the mechanisms by which PTEN is regulated are not fully known. Studies of ovarian cancer cell lines suggest that PTEN may be regulated by PPARγ. We hypothesise that PTEN expression in endometrial cancer may be regulated by PPARγ.
Method
PPAR expression was examined in endometrial cancers by immunohistochemistry and Western blotting. The effects of a PPARγ ligand on PTEN expression were studied in endometrial cancer cell lines.
Results
PPARγ and PTEN expression were both lower in endometrial cancer compared with benign endometrium. The PPARγ ligand Ciglitazone inhibited cell proliferation and induced apoptosis in endometrial cancer cell lines and this corresponded to increased PTEN expression. Addition of a PPARγ antagonist reduced these effects in a dose-dependent manner.
Conclusion
The differential expression of PPARs in endometrial cancers and benign endometrium suggests a potential role in endometrial carcinogenesis and/or growth. Our findings indicate that PTEN expression can be modulated by PPARγ activation and suggest that PPARγ ligands should be considered as potential chemopreventative agents.
