Role of p53 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 Gi and G2 arrest, apoptosis or senescence. We are determining the role of p53 in human mammary epithelial cell (HMEC) senescence. We previously showed that p53 and its target gene p21 are significantly upregulated during senescence in post-selection HMECs. We also showed that cells with reduced p53 or p21 proteins have extended replicative life span. However, compared to p21 RNAi, p53 RNAi expressing cells proliferates for four more population doublings suggesting the role of additional targets of p53 in HMEC senescence. p53 is a - sequence specific transcription factor, which binds to promoter region of various genes related to apoptosis and growth arrest. To identify other targets of p53, we carried out array analysis using Human Transsignal p53 Target gene array (Panomics Inc., Redwood City, CA). Briefly mRNA was prepared from early passage (proliferating) and late passage (senescent) HMECs, biotin labeled, and hybridized to p53 target gene array. Our results indicate that in general, p53 target genes are upregulated in senescent HMECs. We have identified several additional targets of p53 in senescent HMECs. These targets include p63, TSP-l, WiGl, iGF-BP3 and BCL-6. We are further confirming upregulation of these targets by RT PCR and chromatin immunorprecipitation linked PCR (Chip) assay.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA438332
Entities
People
- Goberdhan P. Dimri