
Basal-like breast cancers (BLBCs) are aggressive tumors with high relapse rates and poor survival. We recently reported that >70% of primary BLBCs express the oncogenic transcription/translation factor Y-box binding protein-1 (YB-1) and silencing it with small interfering RNAs (siRNAs) attenuates the growth of BLBC cell lines. To understand the basis of these earlier findings, we profiled YB-1:DNA complexes by chromatin immunoprecipitation (ChIP)-on-chip. Several tumor growth-promoting genes such as MET, CD44, CD49f, WNT and NOTCH family members were identified. In addition, YB-1 and MET are coordinately expressed in BLBC cell lines, as well as in normal human mammary progenitor cells. MET was confirmed to be a YB-1 target through traditional ChIP and gel-shift assays. More specifically, YB-1 binds to -1018 bp on the MET promoter. Silencing YB-1 with siRNA decreased MET promoter activity, transcripts, as well as protein levels and signaling. Conversely, expressing wild-type YB-1 or a constitutively active mutant YB-1 (D102) increased MET expression. Finally, silencing YB-1 or MET attenuated anchorage-independent growth of BLBC cell lines. Together, these findings implicate MET as a target of YB-1 that work in concert to promote BLBC growth.
Chromatin Immunoprecipitation, Hepatocyte Growth Factor, YB-1; Met Receptor; ChIp-on-chip; basal-like breast cancer; mammary progenitors, Gene Expression Profiling, Stem Cells, Nuclear Proteins, Breast Neoplasms, Electrophoretic Mobility Shift Assay, Proto-Oncogene Proteins c-met, DNA-Binding Proteins, Cell Line, Tumor, Proto-Oncogene Proteins, Humans, Female, Receptors, Growth Factor, Breast, Y-Box-Binding Protein 1, RNA, Small Interfering, Promoter Regions, Genetic
Chromatin Immunoprecipitation, Hepatocyte Growth Factor, YB-1; Met Receptor; ChIp-on-chip; basal-like breast cancer; mammary progenitors, Gene Expression Profiling, Stem Cells, Nuclear Proteins, Breast Neoplasms, Electrophoretic Mobility Shift Assay, Proto-Oncogene Proteins c-met, DNA-Binding Proteins, Cell Line, Tumor, Proto-Oncogene Proteins, Humans, Female, Receptors, Growth Factor, Breast, Y-Box-Binding Protein 1, RNA, Small Interfering, Promoter Regions, Genetic
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