Cripto: A Target for Breast Cancer Treatment
Abstract
A majority of cell lines respond to DNA-damaging stimuli such as irradiation by growth arrest, DNA repair and eventually apoptosis of damaged cells. The CADD45 gene family members are involved in these functions, and in cells where TP53 is normal, induction by p53 is the major mechanism for the transcriptional up-regulation of GADD45. However, in the absence of wild-type (wt) pS3, as in a majority of cancer cells, we show that Egr1 immediate early transcription factor plays a major role in stress response. Egr1-null mouse embryo fibroblasts (MEEs) do not respond to UV-C by the induction of GADD45 and are resistant to DNA damaging stress, while in wt MEFs, GADD45 is inducible, resulting in cell death. Egr1 acts as a rapidly inducible tra-nscriptional regulator of CADD45a and b in normal and cancer cell lines independently of p53, thereby substituting as a tumor suppressor in place of p53. Since Egr1 is rarely mutated, this factor becomes an important mediator of cancer therapy by irradiation and chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA438430
Entities
People
- Eileen D. Adamson
Organizations
- Sanford Burnham Prebys Medical Discovery Institute