Role of p53 in Mammary Epithelial Cell Senescence
Abstract
The tumor suppressor p53 plays an important role in a variety of cancers including breast cancer. It inhibits the growth of malignant cells either by inducing G1 arrest, apoptosis, senescence or autophagy. In this career development award, we studied the role of p53 in human mammary epithelial cell (HMEC) senescence and the requirement of p53 inactivation in transformation of HMECs. First, we determined that p53 binding activity increases with senescence in post-selection HMECs, and expression of its targets such as p21 is increased in post-selection senescent cells. We also found that there were no major differences in acetylation or phosphorylation of p53 in pre-selection and post-selection HMECs. However, there is a modest increase in acetylated p53 in post-selection senescent HMECs. Next, we studied the role of p53 in HMEC senescence using RNAi approach. Our studies suggested that p53 or p21 knockdown results in bypass of senescence in HMECs. We also carried out an array analysis of p53 targets in early passage (proliferating) and late passage (senescent) post-selection HMECs. Next, we studied the role of additional targets of p53 in HMEC senescence using RT-PCR analysis and identified additional targets of p53 using ChIP assay. Finally, we studied p53/p21 pathway in BMI1+H-RAS transformed HMECs, and the role of p53 in oncogene-induced senescence (OIS) in HMECs.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2009
- Accession Number
- ADA518262
Entities
People
- Goberdhan P. Dimri