Project description:We report the role of AIB1D4 in early stage breast cancer progression. Using CRISPR editing, we generated isogeneic cell lines that only express AIB1D4 and not full length AIB1 then extracted RNA for sequencing from cell lines and mamary fat pad xenografts in SCID/Beige mice. Data was aligned to Hg19 with STAR and processed with EdgeR.
Project description:The long-non-coding HOX transcript antisense intergenic RNA (HOTAIR) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by HOTAIR in early-stage breast cancer progression. We determined that HOTAIR induces premalignant phenotypic changes by increasing cell proliferation, migration, invasion and in vivo growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by HOTAIR which include bioprocesses related to cell migration, epithelial to mesenchymal transition, extracellular matrix remodeling and activation of HIF1A, AP1 and FGFR signaling pathways among others. Similar pathways were identified as activated in primary invasive breast carcinomas with HOTAIR over-expression. We conclude that HOTAIR over-expression behaves as a positive regulator of cell growth and migration both in normal and DCIS breast cells involved with early-stage breast cancer progression.
Project description: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. This SuperSeries is composed of the following subset Series: GSE9204: Role of CSN5 in breast cancer (siRNA transfections) GSE9205: Role of CSN5 in breast cancer (array CGH) Refer to individual Series