Conditional Pten inactivation in pituitary results in sex-specific prolactinoma formation.

Autor: Flores-Martínez Á; Unidad de Gestión de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain; Inserm U1052, CNRS UMR5286, Cancer Research Center of Lyon, Lyon 1 University, Lyon, France., Ramos-Herrero VD; Unidad de Gestión de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain., Barroso A; Unidad de Gestión de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain., Moreno A; Unidad de Gestión de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain., G-García ME; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, Universidad de Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Córdoba, Spain., Venegas-Moreno E; Unidad de Gestión de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain., Dios E; Unidad de Gestión de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain., Martínez-Barberá JP; Developmental Biology and Cancer Programme, GOS Institute of Child Health, University College London, London, UK., Luque RM; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, Universidad de Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Córdoba, Spain., Soto-Moreno A; Unidad de Gestión de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain. Electronic address: alfonsom.soto.sspa@juntadeandalucia.es., Cano DA; Unidad de Gestión de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain. Electronic address: dcano-ibis@us.es.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2025 Jan; Vol. 1871 (1), pp. 167543. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1016/j.bbadis.2024.167543
Abstrakt: Pituitary tumors, including prolactinomas, present significant clinical challenges that require a deeper understanding of their molecular roots for improved diagnostics and therapies. Here, we investigate the role of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K) pathway in pituitary tumorigenesis using a mouse model. Conditional knockout of Pten in all pituitary cell lineages resulted in prolactinoma formation exclusively in female mice, demonstrating the critical role of PTEN in pituitary homeostasis. While Pten inactivation induced Akt activation in all pituitary cells, only prolactin-producing cells exhibited tumorigenic changes, suggesting specific cell-type effects. Histological and molecular analyses of prolactinomas revealed similarities with human pituitary tumors, such as decreased vascularization and cell adhesion proteins and increased accumulation of cell cycle proteins. Notably, prolactinomas displayed diminished levels of phosphorylated extracellular signal-regulated kinase (ERK), implicating downregulation of ERK in tumorigenesis. Finally, we analyzed PTEN/PI3K activation in a collection of human pituitary tumors. Overall, our study delineates the intricate interplay between the PTEN and ERK signaling pathways, providing insights into sex-specific mechanisms of pituitary tumorigenesis and potential therapeutic strategies for prolactinomas.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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