Role of P53 in Mammary Epithelial Cell Senescence
Annual summary rept. 1 May 2005-30 Apr 2006
EVANSTON NORTHWESTERN HEALTHCARE RESEARCH INST IL
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The tumor suppressor p53 plays an important role in a variety of cancers including breast cancer. In response to oncogenic signals, it induces growth arrest, apoptosis or senescence. We are determining the role of p53 in human mammary epithelial cell HMEC senescence. Previously, we identified several transcriptional targets of p53 using array analysis In this reporting period, we confirmed expression of several of these targets by RT PCR. We also chose several other targets of p53 that are induced by DNA damage. The RT PCR analysis aws carried out using mRNA prepared from young growing early passage and senescent late passage HMECs. Results indicate that while several p53 target genes showed significant upregulation, certain other targets showed no significant upregulation in senescent HMECs suggesting a differential regulation of p53 target genes during senescence in HMECs. We are further studying the regulation of these genes by p53 using chromatin immunoprecipitation linked PCR ChIP. We are also determining the role of these genes in HMECs senescence by RNA interference approach. IGFBP3, TGF , Wig1, HGFL, BCL6, TMEM30A, BTG-2, GADD45A and MDM4 showed the most significant upregulation in senescent HMECs. To identify additional targets of p53 that are induced during HMEC senescence, we are making a ChIP library of p53 target genes using antibodies that are specific to total and phosphop53, and cells that are undergoing cellular senescence.
- Anatomy and Physiology
- Medicine and Medical Research