Journal article
Global Expression Analysis of Endometrial Cancer Cells in Response to Progesterone Identifies New Therapeutic Targets
The Journal of steroid biochemistry and molecular biology, Vol.234, 106399
11/2023
DOI: 10.1016/j.jsbmb.2023.106399
PMCID: PMC11171468
PMID: 37716459
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.
Details
- Title: Subtitle
- Global Expression Analysis of Endometrial Cancer Cells in Response to Progesterone Identifies New Therapeutic Targets
- Creators
- Kristina W Thiel - University of IowaAndreea M Newtson - University of IowaEric J Devor - University of IowaYuping Zhang - University of IowaPaige K Malmrose - University of IowaJianling Bi - University of IowaHaley A Losh - University of IowaSuzy Davies - University of New MexicoLane E SmithJamie PadillaStephanie M Leiva - University of IowaChad E Grueter - University of IowaPatrick Breheny - University of IowaChristy R Hagan - University of Kansas Medical CenterMiles A Pufall - University of IowaJason Gertz - Huntsman Cancer InstituteYan Guo - University of New MexicoKimberly K Leslie - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of steroid biochemistry and molecular biology, Vol.234, 106399
- DOI
- 10.1016/j.jsbmb.2023.106399
- PMID
- 37716459
- PMCID
- PMC11171468
- NLM abbreviation
- J Steroid Biochem Mol Biol
- ISSN
- 0960-0760
- eISSN
- 1879-1220
- Publisher
- Elsevier
- Language
- English
- Electronic publication date
- 09/14/2023
- Date published
- 11/2023
- Academic Unit
- Biostatistics; Cardiovascular Medicine; Radiation Oncology; Craniofacial Anomalies Research Center; Obstetrics and Gynecology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984465558802771
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