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PGR-B expression in the ovary drives ovarian neoplasia and a tumorigenic transcriptome.

ABSTRACT: PGR-B expression in the ovary drives ovarian neoplasia and a tumorigenic transcriptome.

PROVIDER: PRJNA565428 | ENA |

REPOSITORIES: ENA

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PGR-B expression in the ovary drives ovarian neoplasia and a tumorigenic transcriptome.

Project description:Constitutive PGR-B expression in PGR positive cells in the mouse drives ovarian neoplasia. To compare the differences between the PGR-B expressing ovarian neoplasia tissue and age-matched wildtype ovaries, microarray analysis was performed. It was concluded that PGR-B expression promoted a tumorigenic signature distinctly different from wildtype ovarian tissue.

2020-09-10 | GSE137432 | GEO

PGR-B directly binds to promoters of genes important for cell cycle, proliferation, and tumorigenesis within ovarian neoplasia from PGRcre/+mPGRBLsL/+ mice

Project description:Long-term expression of PGR-B in the PGRcre/+mPGRBLsL/+ mice results in ovarian neoplasia as early as 23 weeks of age. Microarray analyses in the ovarian tumors exhibit strong molecular signatures of proliferation and tumorigenesis. In order to identify if PGR-B was directly promoting this tumorigenic agenda, ChIP-Seq was performed on ovarian neoplasia from PGRcre/+mPGRBLsL/+ mice at greater than 7.5 months of age. These data suggest PGR-B directly promotes cell cycle related genes, driving the uncontrolled growth in the ovarian tissue.

2020-09-10 | GSE137548 | GEO

PGR-B is responsible for a proliferative gene signature in ovarian neoplasia in PGR-B expressing mice.

Project description:Constitutive PGR-B expression in PGR positive cells in the mouse drives ovarian neoplasia. Chronic treatment with RU486 reduced tumor growth in these PGR-B expressing mice. To further identify how PGR-B functions to promote sustained tumor growth, PGRcre/+ PGR-BLsL/+ mice with ovarian tumors were administered a chronic-release pellet of RU486 or placebo for 24 hours. Tissue was harvested and RNA was isolated. After comparative analyses, it was concluded that PGR-B promotes cell cycle regulatory genes and oncogenic signaling pathways.

2020-09-10 | GSE137499 | GEO

PGR-B is responsible for a proliferative gene signature in ovarian neoplasia in PGR-B expressing mice.

Project description:PGR-B is responsible for a proliferative gene signature in ovarian neoplasia in PGR-B expressing mice.

| PRJNA565732 | ENA

Gene expression analysis of granulosa cells from animals that are wildtype or knockout for total PGR, PGR-A or PGR-B (RNA-seq)

Project description:Progesterone receptor (PGR) is essential for various functions in the female reproductive tract, especially ovulation in the ovary. PGR consists of two main isoforms, PGR-A and PGR-B, that possess different expression patterns and are responsible for various unique roles in different tissue contexts. While both are present in the reproductive tract, PGR-A is the only one known to be essential for ovulation while PGR-B plays a lesser role in the reproductive tract. However, the specific roles of PGR isoforms on gene expression in peri-ovulatory granulosa cells have not been previously investigated in detail. In this study, we identified the unique role of PGR-A and PGR-B in peri-ovulatory granulosa cells through RNA-seq of knockout mouse models for total PGR (PGR KO) or specific isoforms (PGR-A KO and PGR-B KO)

2022-05-18 | GSE168213 | GEO

PGR-B and ovarian neoplasma

Project description:PGR-B and ovarian neoplasma

| PRJNA565425 | ENA

Genome-wide binding sites of Progesterone receptor (PGR) isoforms PGR-A and PGR-B during differentiation of human endometrial stromal cells

Project description:We report the genome-wide binding sites of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells that express either PGR-A or PGR-B. Progesterone, acting through the progesterone receptors (PGRs), is one of the most critical regulators of endometrial differentiation, known as decidualization, which is a key step toward the establishment of pregnancy. Yet a long-standing unresolved issue in uterine biology is the precise roles played by the major PGR isoforms, PGR-A and PGR-B, during decidualization in the human. Our approach, expressing PGR-A and PGR-B individually after silencing endogenous PGRs in human endometrial stromal cells (HESC), enabled the analysis of the roles of these isoforms separately as well as jointly by ChIP-seq and gene-expression analysis. In order to study the cistromes of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells, we generated primary cultures of human endometrial stromal cells expressing flag tagged PGR-A and PGR-B individually after silencing endogenous PGRs. Input DNA was used as the reference sample.

2015-04-27 | E-GEOD-62475 | biostudies-arrayexpress

Gonadotropin surge-induced expression of progesterone receptor serves the ovary as a trigger of ovulation and a terminator of ovulatory inflammation

Project description:Ovulation is triggered by the gonadotropin surge that induces the expression of two key genes, progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2) in the granulosa cells of preovulatory follicles. Their gene products PGR and PTGS2 activate two separate pathways that are both essential for successful ovulation. Here we show that the PGR plays an additional essential role; attenuate ovulatory inflammation by diminishing the gonadotropin surge-induced Ptgs2 expression. PGR indirectly terminates Ptgs2 expression and PGE2 synthesis in granulosa cells by inhibiting the NF-κB, a transcription factor required for Ptgs2 expression. When the expression of PGR was ablated in the granulosa cells, the ovary undergoes hyperinflammatory condition manifested by excessive PGE2 synthesis, immune cell infiltration, oxidative damage, and neoplastic transformation of ovarian cells. Despite the ovary undergoes ovulations dozens or hundreds of times in one’s lifetime, the repetitive ovulatory inflammations do not leave significant tissue damage in the ovary. The PGR-driven termination of PTGS2 expression may protect ovary from the ovulatory inflammation.

2020-03-07 | GSE145107 | GEO

Genome-wide binding sites of Progesterone receptor (PGR) isoforms PGR-A and PGR-B during differentiation of human endometrial stromal cells

2015-04-27 | GSE62475 | GEO

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

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