Abstract 4206: Identification of transcriptional regulatory motifs that control gene expression in premenopausal women with previous history of breast cancer

Abstract

Abstract Background: Age is an important risk factor for Breast Cancer. Older women have a 50 times greater risk for breast cancer as compared to younger women (under the age of 30 years). Aging is associated with activation of specific transcription factor networks. We hypothesized that premature activation of these programs may predispose to cancer. The aims of this study were 1) to identify active transcription factor networks controlling the expression of specific cancer-related genes in the normal breast and 2) to analyze whether premature activation of this network is associated with neoplastic transformation. Methods: Fresh frozen normal breast tissue of women, under the age of 50 years, with and without history of breast cancer was obtained (ncancer=8, nnon cancer=4). Total RNA was extracted, cDNA annealed and Whole-genome DASL assay (Illumina Corp) was conducted to identify genes that correlated with cancer outcome in premenopausal women. Differential expression analysis was performed using Partek® software program to identify the up or down regulated genes in women with cancer compared to those without. Transcription factors affecting the regulation of genes in patients with cancer were predicted using MotifModeler program (Liu et al). The resulting data was confirmed using qPCR analysis. Results: Whole genome DASL analysis showed differential expression of 34 genes (p-value <0.01). MotifModeler analysis predicted 18 transcription factors as major regulators of gene expression in premenopausal women with previous history of breast cancer. JUNB and FOS were the most significantly altered in this comparison. qPCR pre-validated the over expression of JUNB and FOS in association with cancer development. Further validation studies in an independent cohort are ongoing using Formalin-fixed Paraffin-embedded (FFPE) samples. Conclusion: Gene expression analysis identified transcriptional features of cancer outcome. Differential expression of the JUNB and FOS family of proteins, which are part of AP-1 transcription factor complex, may be correlated with neoplastic transformation in premenopausal women. Breast Cancer Program of the IU Simon Cancer Center funded this project. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4206. doi:1538-7445.AM2012-4206