This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Holland, C. M. Articles by Smith, S. K. Search for Related Content PubMed PubMed Citation Articles by Holland, C. M. Articles by Smith, S. K.

Departments of ¹ Pathology and ² Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, United Kingdom

Requests for reprints: Cathrine M. Holland, Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Box 223, Level 2, Robinson Way, Cambridge CB2 2SW, United Kingdom. Phone: 44-1223-336874; Fax: 44-1223-215327. E-mail: cath.holland{at}obgyn.cam.ac.uk

Endometrial cancer is the most common gynecologic malignancy, frequently arising in association with obesity and diabetes mellitus. To identify gene pathways contributing to endometrial cancer development, we studied the transcriptome of 20 endometrial cancers and 11 benign endometrial tissues using cDNA microarrays. Among the transcript changes identified in endometrial cancer were up-regulation of the nuclear hormone receptors peroxisome proliferator-activated receptors (PPAR) and , whereas retinoid X receptor ß was down-regulated. To clarify the contribution of PPAR to endometrial carcinogenesis, we did experiments on cultured endometrial carcinoma cells expressing this transcript. Treatment with fenofibrate, an activating ligand for PPAR, significantly reduced proliferation and increased cell death, suggesting that altered expression of nuclear hormone receptors involved with fatty acid metabolism leads to deregulated cellular proliferation and apoptosis. These results support further investigation of members of the PPAR/retinoid X receptor pathway as novel therapeutic targets in endometrial cancer.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 3/30/04; revised 5/ 4/04; accepted 5/14/04.