Systematic name M12456
Brief description Cluster 2: genes down-regulated by RB1, CDNK2A [GeneID=1029;5925], and one of the E2Fs (E2F1, E2F2, or E2F3 [GeneID=1869;1870;1871]).
Full description or abstract Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of human cancer. The core members of this pathway include the tumor suppressor protein, pRB, which through binding to a number of cellular proteins, most notably members of the E2F transcription factor family, regulates progression through the cell division cycle. With the aim of identifying transcriptional changes provoked by deregulation of the pRB pathway, we have used cell lines that conditionally express a constitutively active phosphorylation site mutant of pRB (pRBDeltaCDK) or p16INK4A (p16). The expression of pRBDeltaCDK and p16 resulted in significant repression and activation of a large number of genes as measured by high density oligonucleotide array analysis. Transcriptional changes were found in genes that are essential for DNA replication and cell proliferation. In agreement with previous results, we found a high degree of overlap between genes regulated by p16 and pRB. Data we have obtained previously for E2F family members showed that 74 of the genes repressed by pRB and p16 were induced by the E2Fs and 23 genes that were induced by pRB and p16 were repressed by the E2Fs. Thus, we have identified 97 genes as physiological targets of the pRB pathway, and the further characterization of these genes should provide insights into how this pathway controls proliferation. We show that Gibbs sampling detects enrichment of several sequence motifs, including E2F consensus binding sites, in the upstream regions of these genes and use this enrichment in an in silico filtering process to refine microarray derived gene lists.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 12923195   Authors: Vernell R,Helin K,Müller H
Exact source Table 1: cluster 2
Related gene sets (show 1 additional gene sets from the source publication)

(show 10 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Kevin Vogelsang (Broad Institute)
Source platform HG_U95Av2
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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