Role of p53 in Mammary Epithelial Cell Senescence
Abstract
Preselect ion and postselection human mammary epithelial cells (HMECs) differ greatly in replicative potential. In this report, we studied the role of p53 in senescence of preselection and postselection HMECs. Western blot analysis of early (proliferating) and late (senescing) preselection and postselection HMECs showed that postselection HMECs have higher level of p53, which is upregulated during senescence. postselection HMECs also showed higher expression of p53 target gene p21. On the other hand, there was no increase in p53 level and its target gene p21 in senescent preselection cells. DNA binding assays using p53 binding site of p21 promoter and extracts prepared from early and late passage postselection cells suggest that p53 binding activity increases with senescence in postselection HMECs. We also studied posttranslational modifications of p53 in HMECs using antibodies specific for various phosphorylated and acetylated form of p53. Results suggest there are no major differences in acetylation or phosphorylation of p53 in preselection and postselection HMECs. However, postselection HMECs contained higher level of p53 phosphorylated at Ser-38. Taken together, these results suggest p53 plays an important role in senescence of postselection HMECs, but not in senescence of preselection HMECs.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA417603
Entities
People
- Goberdhan P. Dimri