| First Author | Krones-Herzig A | Year | 2005 |
| Journal | Cancer Res | Volume | 65 |
| Issue | 12 | Pages | 5133-43 |
| PubMed ID | 15958557 | Mgi Jnum | J:99386 |
| Mgi Id | MGI:3582090 | Doi | 10.1158/0008-5472.CAN-04-3742 |
| Citation | Krones-Herzig A, et al. (2005) Early growth response 1 acts as a tumor suppressor in vivo and in vitro via regulation of p53. Cancer Res 65(12):5133-43 |
| abstractText | The early growth response 1 (Egr1) gene is a transcription factor that acts as both a tumor suppressor and a tumor promoter. Egr1-null mouse embryo fibroblasts bypass replicative senescence and exhibit a loss of DNA damage response and an apparent immortal growth, suggesting loss of p53 functions. Stringent expression analysis revealed 266 transcripts with >2-fold differential expression in Egr1-null mouse embryo fibroblasts, including 143 known genes. Of the 143 genes, program-assisted searching revealed 66 informative genes linked to Egr1. All 66 genes could be placed on a single regulatory network consisting of three branch points of known Egr1 target genes: TGFbeta1, IL6, and IGFI. Moreover, 19 additional genes that are known targets of p53 were identified, indicating that p53 is a fourth branch point. Electrophoretic mobility shift assay as well as chromatin immunoprecipitation confirmed that p53 is a direct target of Egr1. Because deficient p53 expression causes tumors in mice, we tested the role of Egr1 in a two-step skin carcinogenesis study (144 mice) that revealed a uniformly accelerated development of skin tumors in Egr1-null mice (P < 0.005). These studies reveal a new role for Egr1 as an in vivo tumor suppressor. |
