NF-kappaB-Mediated Repression of GADD153/CHOP: A Role in Breast Cancer Initiation
Abstract
Factors that control initiation of breast cancer are largely unknown. Mammary epithelial cells usually have a limited life span, which is governed by a balance between pro-survival and pro-apoptotic proteins. Imbalance in the expression level of these proteins, particularly pro-survival factors, is believed to promote immortalization and transformation of mammary epithelial cells. The transcription factor NF-%B can alter the ratio between pro-survival and pro- apoptotic proteins as it can induce the expression of several pro-survival genes and decrease the expression of pro-apoptotic genes. Our studies have shown that NF-kB upregulates pro-survival genes TRAF-l, cIAP-2 and Mn-SOD and inhibits the expression of pro-apoptotic gene GADDl53/CHOP. In this award, we are investigating whether NF-kB mediated repression of GADDl53 expression plays any role in breast cancer initiation upon DNA damage by environmental toxicants. Our approach is to overexpress the NF-KB subunit p65 in immortalized mammary epithelial cell line MCF-lOA and evaluate transformation of these cells by environmental toxicants such as methyl methanesulfonate. Soft agar and matrigel assays will be used to measure transformation. Our initial attempts to obtain MCF-l0A cells overexpressing the p6S subunit using plasmid-based vectors was not successful. Therefore, we have generated retrovirus that can transduce p65 to MCF-lOA cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA410456
Entities
People
- Harikrishna Nakshatri
- Hui L. Chua
Organizations
- Indiana University