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MacroH2A1.2 inhibits prostate cancer-induced osteoclastogensis through cooperation with HP1a and H1.2

ABSTRACT: Prostate cancer cells frequently metastasize to bone and secrete signaling factors that can lead to osteoclast differentiation. However, the mechanism of regulation of ostecolastostogenesis by soluble secretory factors from prostate cancer is largely unknown. MacroH2A effect the chromatin function and can potentially attenuate the prostate cancer induced ostoclastogenesis. To study the effect of mH2A1.2 on osteclastogenesis , we used genome wide gene expression studies in wild type and mH2A1.2 knockout DU154 – prostate cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107636 | GEO | 2023/03/01

REPOSITORIES: GEO

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MacroH2A1.2 inhibits prostate cancer-induced osteoclastogensis through cooperation with HP1a and H1.2

Project description:MacroH2A1.2 inhibits prostate cancer-induced osteoclastogensis through cooperation with HP1a and H1.2

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MacroH2A1.2 inhibits prostate cancer-induced osteoclastogenesis through cooperation with HP1? and H1.2.

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Cooperation between Androgen Receptor and Polycomb in oncogenic transformation

Project description:Androgen receptor (AR) is a hormone-activated transcription factor that plays important roles in prostate development, function, as well as malignant transformation. The downstream pathways of AR, however, are incompletely understood. AR has been primarily known as a transcriptional activator inducing prostate-specific gene expression. Through integrative analysis of genome-wide AR occupancy and androgen-regulated gene expression, here we report AR as a globally acting transcriptional repressor. This repression is mediated by androgen responsive elements (ARE) and dictated by Polycomb group protein EZH2 and repressive chromatin remodeling. In embryonic stem cells, AR-repressed genes are occupied by EZH2 and harbor bivalent H3K4me3 and H3K27me3 modifications that are characteristic of differentiation regulators, the silencing of which maintains the undifferentiated state. Concordantly, these genes are silenced in castration-resistant prostate cancer rendering a stem cell-like lack of differentiation and tumor progression. Collectively, our data reveal an unexpected role of AR as a transcriptional repressor inhibiting non-prostatic differentiation and, upon excessive signaling, resulting in cancerous de-differentiation. It provides an innovative mechanism for castration resistance and highlights novel therapeutic strategies to treat advanced prostate cancer. Keywords: Genetic Modification compare gene expression in different cell lines with or without androgen treatment or EZH2 knockdown

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Homo sapiens

Project description:Prostate Cancer Field Effect

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Homo sapiens

Project description:Towards understanding breast cancer mechanisms to metastasize

| PRJNA205399 | ENA

Cooperation between Androgen Receptor and Polycomb in oncogenic transformation

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The histone variant macroH2A modulates inflammatory response in cancer [UMI-4C]

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2022-06-21 | GSE203475 | GEO

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