Identification of genes responsible for RelA-dependent proliferation arrest in HMEC conditionally expressing RelA
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ABSTRACT: Immuno-histochemistry for RelA in breast tumors revealed a range of staining intensity and negative correlation between RelA levels and proliferation-index in estrogen receptor-positive tumors. Conditional expression of RelA arrested proliferation in primary mammary and fallopian tube epithelial cells. RelA dependent CDK4 downregulation was responsible for activating the G1/S checkpoint and cell cycle arrest. RelA target genes, including Interferon Response Factors (IRF), were up-regulated in the arrested cells. Among the IRFs, IRF1 expression correlates with RelA expression. Suppressing IRF1 restored CDK4 levels and rescued RelA-dependent proliferation arrest analogous to abrogating the G1/S checkpoint or restoring CDK4 levels. Apart from cyclins, regulation of CDK4 by the RelA-IRF1 transcriptional network controls proliferation of breast tumors and predicts sensitivity to a CDK4/6 inhibitor.
ORGANISM(S): Homo sapiens
PROVIDER: GSE65040 | GEO | 2015/09/26
SECONDARY ACCESSION(S): PRJNA272772
REPOSITORIES: GEO
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