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Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis

ABSTRACT: Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis

PROVIDER: PRJNA912136 | ENA |

REPOSITORIES: ENA

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Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis

Project description:In the current study, we combined a multi-fluorescent reporter mouse model with a conditional knockout mouse model, in which the tumor suppressor genes Pten and p27 were deleted in GCs, to perform cell lineage tracing of mutant GCs. We found that only 30% of ovaries with substantial mutant GCs developed into GCTs that derived from a single mutant GC. In-depth molecular analysis of the process of tumorigenesis demonstrated that up-regulation of immune evasion genes Cd24a and Cd47 led, in part, to the transition of mutant GCs to GCTs. Therefore, treatment with the Cd47 inhibitor RRX-001 was tested and found to efficiently suppress the growth of GCTs in vivo.

2023-05-10 | GSE220947 | GEO

Granulosa cell tumorigenesis

Project description:Comparison of global changes in ovarian transcriptomes uniquely associated with either granulosa cell tumors or luteomas, and identification of new markers for this tumor phenotype. Luteinizing hormone hypersecreting mice studied. Keywords: other

2003-07-16 | GSE499 | GEO

Zearalenone exposure enhanced the expression of tumorigenesis genes in donkey granulosa cells via the PTEN/PI3K/AKT signaling pathway

Project description:We investigated the biological effects of ZEA exposure on donkey granulosa cells by using RNA-seq analysis. ZEA at 10 and 30 μM were administered to granulosa cells within 72 hours of in vitro culture. ZEA at 10 μM significantly altered the tumorigenesis associated genes in donkey granulosa cells. Exposure to 10 and 30 μM ZEA treatment significantly reduced mRNA expression of PTEN, TGFβ, ATM, and CDK2 genes, particularly, the ZEA treatment significantly increased the expression of PI3K and AKT genes. Furthermore, immunofluorescence, RT-qPCR, and Western blot analysis verified the gene expression of ZEA-exposed granulosa cells. Collectively, these results demonstrated the deleterious effect of ZEA exposure on the induction of ovarian cancer related genes via the PTEN/PI3K/AKT signaling pathway in donkey granulosa cells in vitro.

2018-07-12 | GSE116950 | GEO

Tracing tumorigenesis in a solid tumor model at single-cell resolution

Project description:Tracing tumorigenesis in a solid tumor model at single-cell resolution

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granulosa cell tumor vs normal granulosa cells

Project description:mRNA expression profiling in human granulosa cell tumor cell line and normal granulosa cells

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Akt1 depletion in murine ovarian granulosa cells reveals known and novel molecular and cellular processes dependent on this kinase

Project description:The PI3K/AKT signaling pathway is known to regulate a broad range of cellular processes and it is often altered in several types of cancers. Recently, somatic AKT1 mutations leading to a strong activation of this kinase have been reported in juvenile granulosa cell tumors. However, the molecular role of AKT1 in the ovary is still poorly understood. To get insights into its ovarian function, we depleted Akt1 in murine primary granulosa cells, a supporting cell lineage, and assessed the molecular consequences at both the transcript and protein levels. We were able to corroborate the involvement of AKT1 in metabolism, apoptosis, cell cycle or cytoskeleton regulation in granulosa cells. Consistently, we showed that established granulosa cells depleted for Akt1 exhibited increased velocity and altered directional persistent migration. This study also allowed us to uncover new direct and indirect targets of the kinase. Indeed, a series of proteins involved in intracellular transport and mitochondrial physiology were also significantly affected by Akt1 depletion. Using in silico analyses, we also propose a set of kinases and transcription factors that can mediate the action of AKT1 on the deregulated transcripts and proteins. Taken altogether, our results provide a resource of direct and indirect AKT1 targets in the ovary and may shed light on the molecular events driving tumorigenesis owing to its mutations in granulosa cells.

2019-04-30 | PXD012548 | Pride

Human granulosa

Project description:Human granulosa

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Capnocytophaga granulosa

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Human Granulosa Cells Proteome

Project description:Human granulosa cells are follicular cells surrounding the oocyte. Human granulosa cells are retrieved during in vitro fertilization a process where patients undergo hormonal stimulation including FSH and LH/hCG stimulation. Under the influence of the luteinizing hormone (LH) a process called luteinization they differentiate to luteal cells and contribute to the corpus luteum. Therefore, this cellular system is a good model for human corpus luteum (CL). To study processes within the human CL, IVF-derived GCs from patients were cultured for two to five days and then analyzed with mass spectrometry based shotgun proteomics.

2019-03-07 | PXD010658 | Pride

HP1 are dispensable for liver development and functions but are essential to prevent liver tumorigenesis

Project description:HP1 are dispensable for liver development and functions but are essential to prevent liver tumorigenesis

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