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Constitutive expression of the progesterone receptor isoforms promotes the hormone-dependent of the ovarian neoplasma

ABSTRACT: Constitutive expression of the progesterone receptor isoforms promotes the hormone-dependent of the ovarian neoplasma

PROVIDER: PRJNA564984 | ENA |

REPOSITORIES: ENA

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Constitutive expression of the progesterone receptor isoforms promotes the hormone-dependent of the ovarian neoplasma

Project description:At 23 weeks old, the PGR-cre induced PGR-B constitute expression promoted the ovarian tumor progression in female mice. The transcriptomice changes can be divided into two subclass, each represented stage I and stage II ovarian tumor we observed in this study. Stage I is the early stage of ovarian tumor with small amount of PGR-B positve cells observed in the ovary but relatively normal ovarian structures. As expected, stage I transcriptome is similar to the Pgrcre/+ ovary but already exhibited 364 differentiated expression genes suggesting the early transformation of PGR-B positive cells to the neoplasma tissues. Stage II contains snumerous large pleomorphic cells, sometimes well circumscribed tumor, and most of these cells are PGR positve, but still maintains some normal ovarian functions. Stage II exibited 3129 differentiated expression genes that are involved in tumorigenesis pathways such as activated PI3K/AKT signaling, altered cell cycle pathways.

2020-09-10 | GSE137269 | GEO

Constitutive expression of progesterone receptor isoforms promotes the development of hormone-dependent ovarian neoplasms.

Project description:Differences in the relative abundances of the progesterone receptor (PGR) isoforms PGRA and PGRB are often observed in women with reproductive tract cancers. To assess the importance of the PGR isoform ratio in the maintenance of the reproductive tract, we generated mice that overexpress PGRA or PGRB in all PGR-positive tissues. Whereas few PGRA-overexpressing mice developed reproductive tract tumors, all PGRB-overexpressing mice developed ovarian neoplasms that were derived from ovarian luteal cells. Transcriptomic analyses of the ovarian tumors from PGRB-overexpressing mice revealed enhanced AKT signaling and a gene expression signature similar to those of human ovarian and endometrial cancers. Treating PGRB-overexpressing mice with the PGR antagonist RU486 stalled tumor growth and decreased the expression of cell cycle-associated genes, indicating that tumor growth and cell proliferation were hormone dependent in addition to being isoform dependent. Analysis of the PGRB cistrome identified binding events at genes encoding proteins that are critical regulators of mitotic phase entry. This work suggests a mechanism whereby an increase in the abundance of PGRB relative to that of PGRA drives neoplasia in vivo by stimulating cell cycling.

| S-EPMC10251233 | biostudies-literature

Comparative analysis of the Progesterone Receptor interactome in the human ovarian granulosa cell line KGN and other female reproductive cells

Project description:The nuclear steroid hormone receptor Progesterone Receptor (PGR) is expressed in granulosa cells in the ovarian follicle in a tightly regulated pattern in response to the surge of Luteinizing Hormone (LH) that stimulates ovulation. PGR plays a critical role in mediating ovulation in response to LH, however the mechanism for this is still unknown. Using the KGN human granulosa cell line expressing the primary PGR isoforms PGR-A or PGR-B, we performed immunoprecipitation-mass spectrometry to identify novel interacting proteins that regulate PGR function in these ovary-specific target cells. Proteomic analysis revealed protein interactions with both PGR isoforms that were gained (e.g. transcriptional coactivators) or lost (e.g. chaperone proteins) in response to the PGR agonist R5020. Additionally, isoform-specific interactions, including different families of transcriptional regulators, were identified. Comparison with published datasets of PGR interacting proteins in human breast cancer cell lines and decidualised endometrial stromal cells demonstrated a remarkable number of tissue-specific interactions, shedding light on how PGR can maintain diverse functions in different tissues. In conclusion, our dataset provides new insights into ovary-specific PGR transcriptional mechanisms.

2025-05-06 | PXD056566 | Pride

Mouse mammary epithelial and stromal cells: Hormone Treated vs. Vehicle Control

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The role of epithelial Progesterone Receptor Isoforms in embryo implantation

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Progesterone Receptor Isoforms, Agonists and Antagonists Differentially Reprogram Estrogen Signaling.

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Project description:Transcriptional profiling of different mouse mammary cellular compartments (basal, luminal and stromal) under define hormone treatments: estrogen, progesterone, estrogen plus progesterone and the vehicle control. Goal was to determine the effect of ovarian hormones on mammary cellular compartment gene expression. Four-condition experiment within each cellular compartment. vehicle vs. estrogen, progesterone and estrogen plus progesterone. Biological replicates: 3 vehicle control, 4 estrogen treatment, 3 progesterone treatment, 4 estrogen plus progesterone treatment in each epithelial compartment (luminal, basal). 3 vehicle control, 3 estrogen, 3 progesterone, 3 estrogen plus progesterone in the stromal compartment.

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The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-ePRAoe_ePRBoe_LE]

Project description:The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-ePRAoe_ePRBoe_LE]

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Project description:The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-Foxo1dd_LE]

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Project description:Here we show that ovarian progesterone is a crucial endogenous factor inducing metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC). To examine the molecular signaling pathways underlying progesterone (P4)-induced HGSC development, we performed gene-expression profiling using RNA sequencing.

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