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Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.
Thiel, Kristina W; Newtson, Andreea M; Devor, Eric J; Zhang, Yuping; Malmrose, Paige K; Bi, Jianling; Losh, Haley A; Davies, Suzy; Smith, Lane E; Padilla, Jamie; Leiva, Stephanie M; Grueter, Chad E; Breheny, Patrick; Hagan, Christy R; Pufall, Miles A; Gertz, Jason; Guo, Yan; Leslie, Kimberly K.
Afiliación
  • 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.
  • 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.
  • 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.
  • Zhang Y; Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
  • Malmrose PK; Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
  • Bi J; Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
  • Losh HA; Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
  • Davies S; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • 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.
  • 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.
  • Leiva SM; Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
  • Grueter CE; Department of Internal Medicine, Carver College of Medicine, the University of Iowa, Iowa City, IA, USA.
  • 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.
  • Hagan CR; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA.
  • Pufall MA; Department of Biochemistry and Molecular Biology, University of Iowa, Iowa City, IA, USA.
  • Gertz J; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  • Guo Y; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
  • 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
J Steroid Biochem Mol Biol ; 234: 106399, 2023 11.
Article en En | MEDLINE | ID: mdl-37716459
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Quinasas Janus Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: J Steroid Biochem Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Quinasas Janus Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: J Steroid Biochem Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido