Unknown,Transcriptomics,Genomics,Proteomics

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Role of CSN5 in breast cancer (siRNA transfections)

ABSTRACT: CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. A genetic modification design type is where an organism(s) has had genetic material removed, rearranged, mutagenized or added, such as knock out. Computed

ORGANISM(S): Homo sapiens

SUBMITTER: Adam Adler

PROVIDER: E-GEOD-9204 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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CSN5 isopeptidase activity links COP9 signalosome activation to breast cancer progression.

Adler Adam S AS Littlepage Laurie E LE Lin Meihong M Kawahara Tiara L A TL Wong David J DJ Werb Zena Z Chang Howard Y HY

Cancer research 20080101 2

CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here, we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 ...[more]

PMID: 18199546

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Role of CSN5 in breast cancer (siRNA transfections)

Publications

CSN5 isopeptidase activity links COP9 signalosome activation to breast cancer progression.

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