Abstract
Abstract B009: Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets
Clinical cancer research, Vol.30(5_Supplement), pp.B009-B009
03/01/2024
DOI: 10.1158/1557-3265.ENDO24-B009
Abstract
Abstract Progesterone prevents development of endometrial cancers through its receptor (PR) although the molecular mechanisms have yet to be fully characterized. In this study, we performed a global analysis of gene regulation by progesterone using human endometrial cancer cells that expressed PR endogenously or exogenously. We found progesterone strongly inhibits multiple components of the platelet derived growth factor receptor (PDGFR), Janus kinase (JAK), signal transducer and activator of transcription (STAT) pathway through PR. The PDGFR/JAK/STAT pathway signals to control numerous downstream targets including AP-1 transcription factors Fos and Jun. Treatment with inhibitors of the PDGFR/JAK/STAT pathway significantly blocked proliferation in multiple novel patient-derived organoid models of endometrial cancer, and activation of this pathway was found to be a poor prognostic signal for the survival of patients with endometrial cancer from The Cancer Genome Atlas. Our study identifies this pathway as central to the growth-limiting effects of progesterone in endometrial cancer and suggests that inhibitors of PDGFR/JAK/STAT should be considered for future therapeutic interventions. Citation Format: Kristina Thiel, Andreea Newtson, Eric Devor, Yuping Zhang, Paige K. Malmrose, Haley Losh, Suzy Davies, Lane E. Smith, Jamie Padilla, Stephanie Leiva, Christy Hagan, Miles Pufall, Jay Gertz, Yan Guo, Kimberly K. Leslie. Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B009.
Details
- Title: Subtitle
- Abstract B009: Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets
- Creators
- Kristina Thiel - University of IowaAndreea Newtson - University of Nebraska at OmahaEric Devor - University of IowaYuping Zhang - University of IowaPaige K. Malmrose - University of IowaHaley Losh - University of IowaSuzy Davies - University of New MexicoLane E. SmithJamie PadillaStephanie Leiva - University of IowaChristy Hagan - University of Kansas Medical CenterMiles Pufall - University of IowaJay GertzYan Guo - University of New MexicoKimberly K. Leslie - University of New Mexico
- Resource Type
- Abstract
- Publication Details
- Clinical cancer research, Vol.30(5_Supplement), pp.B009-B009
- DOI
- 10.1158/1557-3265.ENDO24-B009
- ISSN
- 1557-3265
- eISSN
- 1557-3265
- Language
- English
- Date published
- 03/01/2024
- Academic Unit
- Obstetrics and Gynecology; Chemical and Biochemical Engineering; Biochemistry and Molecular Biology
- Record Identifier
- 9984648259802771
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