[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-381223-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-381223-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","the-role-of-peroxisome-proliferator-activated-receptors-in-endometrial-cancer","The Role of Peroxisome Proliferator-Activated Receptors in Endometrial Cancer","","Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins that regulate gene expression. A literature review across MEDLINE and LIVIVO identified 27 relevant studies from 2000 to 2023. PPAR-β and PPAR-δ/α isoforms appeared upregulated, while PPAR-γ levels were reported as significantly lower in endometrial cancer cells. 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The Role of Peroxisome Proliferator-Activated Receptors in Endometrial Cancer. Int.  \nJ. Mol. Sci. 2023, 24, 9190. [https://](https://)[ ](https://)[doi.org/10.3390/ijms24119190](doi.org/10.3390/ijms24119190)  \nAcademic Editor: Kuo-Hu Chen  \nReceived: 8 May 2023  \nRevised: 19 May 2023  \nAccepted: 23 May 2023  \nPublished: 24 May 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 First Department of Pathology, Medical School, National and Kapodistrian University of Athens,  \n75 Mikras Asias Street, Bld 10, Goudi, 11527 Athens, Greece; [kliovr1@gmail.com](kliovr1@gmail.com) (K.V.)  \n2 Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Bld 16, Goudi, 11527 Athens, Greece  \n* Correspondence: [ktrougkos@med.uoa.gr](ktrougkos@med.uoa.gr) (C.T.); [stamtheo@med.uoa.gr](stamtheo@med.uoa.gr) (S.T.)  \nAbstract: Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins which regulate gene expression. In order to investigate the role of PPARs in endometrial cancer, we conducted a literature review using the MEDLINE and LIVIVO databases and were able to identify 27 relevant studies published between 2000 and 2023 . The PPAR􀀋 and PPAR􀀌/􀀎 isoforms seemed tobe upregulated, whereas PPAR􀀍 levels were reported to be significantly lower in endometrial cancer cells. Interestingly, PPAR agonists were found to represent potent anti-cancer therapeutic alternatives. In conclusion, PPARs seem to play a significant role in endometrial cancer.  \nKeywords: peroxisome proliferator-activated receptor; PPAR; endometrial cancer  \n1. Introduction  \nEndometrial cancer represents the most common malignant female genital tract tumor in the United States. According to the American Cancer Society, about 66,200 new cases of cancer of the uterine body will be diagnosed and about 13,030 women will die from cancers of the body of the uterus in the United States in 2023 [1] . Endometrial cancer most frequently affects postmenopausal women aged 55–64, with the median age at diagnosis being 63 years [2] . Endometrial cancer may be subdivided into two distinct histopathologic categories: type I endometrial carcinoma originating from atypical hyperplasia of the endometrium and type II endometrial cancer of non-endometrioid histology [3] . Type I endometrial carcinoma is directly associated with long-term exposure to high estrogen levels and correlates with Phosphatase and TENsin homolog (PTEN) inactivation by mutation, microsatellite instability, as well as mutations of Kirsten RAt Sarcoma virus (KRAS),􀀌-catenin, and/or human MutL Homolog 1 (hMLH1)/MutS Homolog 2 (MSH2) . Type II endometrial cancer is mostly estrogen independent, arises from atrophic endometrium in postmenopausal patients, and is associated with p53 mutations, display inactivation of p16 and E-cadherin, alongside Human Epidermal growth factor Receptor 2 (HER2) amplification [4,5] . While surgery is suggested as a monotherapy for low-risk endometrial malignancies, adjuvant chemotherapy needs to be offered to patients with high–intermediate-or high-risk endometrial cancer, as well as advanced and/or recurrent disease [6] . Combined chemotherapy with carboplatin and paclitaxel embodies the first-line chemotherapeutic regimen, followed by chemotherapeutic ag","cbCaicpLh0oANJ3P","https://ap.wps.com/l/cbCaicpLh0oANJ3P","pdf",1172839,12,"English","# Introduction\n## Endometrial cancer categories and clinical management\n# PPAR biology and regulatory mechanisms","[{\"question\":\"What are PPARs and what do they do in cells?\",\"answer\":\"PPARs are fatty acid-activated nuclear receptors that regulate gene expression. They function as ligand-regulated transcription factors by binding DNA response elements and forming heterodimers with RXRs.\"},{\"question\":\"What changes in PPAR isoforms were reported in endometrial cancer?\",\"answer\":\"The review reports that PPAR-β and PPAR-δ/α isoforms seemed upregulated. In contrast, PPAR-γ levels were reported to be significantly lower in endometrial cancer cells.\"},{\"question\":\"How might PPAR agonists be used in endometrial cancer therapy?\",\"answer\":\"PPAR agonists were identified as potent anti-cancer therapeutic alternatives. The findings support PPARs as significant contributors to endometrial cancer and potential treatment targets.\"}]","The Role of Peroxisome Proliferator-Activated Receptors in Endometrial Cancer | PDF",1790244266]