Human Gene Set: ODONNELL_TARGETS_OF_MYC_AND_TFRC_DN


Standard name ODONNELL_TARGETS_OF_MYC_AND_TFRC_DN
Systematic name M6792
Brief description Genes up-regulated in P493-6 cells (B lymphocyte, Burkitt's lymphoma model) by MYC [GeneID=4609] and down-regulated by RNAi knockdown of TFRC [GeneID=7037].
Full description or abstract Overexpression of transferrin receptor 1 (TFRC1), a major mediator of iron uptake in mammalian cells, is a common feature of human malignancies. Therapeutic strategies designed to interfere with tumor iron metabolism have targeted TFRC1. The c-Myc oncogenic transcription factor stimulates proliferation and growth by activating thousands of target genes. Here we demonstrate that TFRC1 is a critical downstream target of c-Myc. Using in vitro and in vivo models of B-cell lymphoma, we show that TFRC1 expression is activated by c-Myc. Chromatin immunoprecipitation experiments reveal that c-Myc directly binds a conserved region of TFRC1. In light of these findings, we sought to determine whether TFRC1 is required for c-Myc-mediated cellular proliferation and cell size control. TFRC1 inhibition decreases cellular proliferation and results in G1 arrest without affecting cell size. Consistent with these findings, expression profiling reveals that TFRC1 depletion alters expression of genes that regulate the cell cycle. Furthermore, enforced TFRC1 expression confers a growth advantage to cells and significantly enhances the rate of c-Myc-mediated tumor formation in vivo. These findings provide a molecular basis for increased TFRC1 expression in human tumors, illuminate the role of TFRC1 in the c-Myc target gene network, and support strategies that target TFRC1 for cancer therapy.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16508012   Authors: O'Donnell KA,Yu D,Zeller KI,Kim JW,Racke F,Thomas-Tikhonenko A,Dang CV
Exact source Table 7BS
Related gene sets (show 3 additional gene sets from the source publication)

(show 23 gene sets from any of these authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform or
identifier namespace		 AFFY_HG_U133
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 46 genes
Gene families ? Categorize these 46 genes by gene family
Show members (show 58 source identifiers mapped to 46 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.