The Breast Cancer DNA Interactome

Abstract

Abstract : With the development of new methodologies has come a greater appreciation of how genes are able to interact with distal regulatory elements. Gene transcription may be regulated by remote enhancer regions through chromosome looping. The role that higher order chromatin organization plays in cancer progression and metastasis is not yet fully understood. Our major goal has been to characterize physical interactions among selected breast cancer gene loci in normal and malignant mammary cell lines. During the past year, we used IGFBP3, a gene that has been involved in breast cancer pathogenesis, as bait in a 4C-seq experiment comparing normal breast cells (HMEC) and two different breast cancer cell lines (MCF7, an ER positive cell line and MDA-MB-231, a triple negative cell line). We found that in HMEC the genes BCAS1-4 (breast carcinoma amplified sequence 1- 4) were found in the top 10 most significantly enriched regions for interactions with IGFBP3. We also found EGFR (epidermal growth factor receptor), a gene that has also been implicated in cancer, to interact significantly with IGFBP3 in all three samples. These data suggest an important role for chromosomal interactions in the pathogenesis of breast cancer.