Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.

Female Humans Janus Kinases Progesterone / pharmacology Signal Transduction STAT Transcription Factors / genetics Endometrial Neoplasms / drug therapy
Endometrial cancer Fos Janus kinase (JAK) Jun Platelet derived growth factor receptor (PDGFR) Progesterone receptor (PR) Signal transducer and activator of transcription (STAT)

Journal

The Journal of steroid biochemistry and molecular biology
ISSN: 1879-1220
Titre abrégé: J Steroid Biochem Mol Biol
Pays: England
ID NLM: 9015483

Informations de publication

Date de publication:
11 2023
Historique:
received: 31 07 2023
revised: 06 09 2023
accepted: 12 09 2023
medline: 6 11 2023
pubmed: 17 9 2023
entrez: 16 9 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.jsbmb.2023.106399 PMID: 37716459
pubmed: 37716459
pii: S0960-0760(23)00154-1
doi: 10.1016/j.jsbmb.2023.106399
pii:
doi:

Substances chimiques

Janus Kinases EC 2.7.10.2
Progesterone 4G7DS2Q64Y
STAT Transcription Factors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106399

Subventions

Organisme : NCI NIH HHS
ID : F31 CA210610
Pays : United States
Organisme : NCI NIH HHS
ID : K22 CA263783
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA265793
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG008974
Pays : United States

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest KWT is a cofounder of Immortagen, Inc. All others authors delcar they have no financial interests.

Auteurs

Kristina W Thiel (KW)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.

Andreea M Newtson (AM)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Obstetrics and Gynecology, University of Nebraska, Omaha, NE, USA.

Eric J Devor (EJ)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.

Yuping Zhang (Y)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

Paige K Malmrose (PK)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

Jianling Bi (J)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

Haley A Losh (HA)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

Suzy Davies (S)

Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Lane E Smith (LE)

Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.

Jamie Padilla (J)

Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.

Stephanie M Leiva (SM)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

Chad E Grueter (CE)

Department of Internal Medicine, Carver College of Medicine, the University of Iowa, Iowa City, IA, USA.

Patrick Breheny (P)

Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.

Christy R Hagan (CR)

Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA.

Miles A Pufall (MA)

Department of Biochemistry and Molecular Biology, University of Iowa, Iowa City, IA, USA.

Jason Gertz (J)

Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

Yan Guo (Y)

University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.

Kimberly K Leslie (KK)

Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA; Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA. Electronic address: kkleslie@unm.salud.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Global expression analysis of endometrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › Janus kinases › Global expression analysis of endometrial...
questionsmedicales.fr › Hormones gonadiques › Hormones sexuelles stéroïdiennes › Congénères de la progestérone › Progestérone › Global expression analysis of endometrial...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Global expression analysis of endometrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription STAT › Global expression analysis of endometrial...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital féminin › Tumeurs de l'utérus › Tumeurs de l'endomètre › Global expression analysis of endometrial...