BioProject

Gene expression differences, combined with distinct patterns of genomic rearrangements and epigenetic modifications constitute the bases of molecular classification of breast cancer. More...

Gene expression differences, combined with distinct patterns of genomic rearrangements and epigenetic modifications constitute the bases of molecular classification of breast cancer. Molecular subtypes may originate from different cell lineages in the mammary gland, but also from the early activation of oncogenes that may drive the establishment of these molecular subtypes. However, in the natural history of human cancer, it is difficult to discriminate between these two factors : cell lineage and initial oncogenic alterations. In this work, we designed an experimental strategy aiming at determining whether activation of distinct oncogenic pathways in human mammary epithelial cells (HMEC) could lead to different patterns of genetic and epigenetic changes. This work suggests that the early activation of oncogenes is an important determinant of the establishment of breast cancer molecular subtypes along with cell lineage origin. Overall design: In this work, we overexpressed by retroviral transduction three oncogenes WNT1, CCNE1 and RASv12, known to activate different oncogenic pathways, in shp53 immortalized human HMECs and monitored epigenetic and genetic changes at different steps of cell progression. All samples are in biological duplicates. Primary HMECs are named R2. Two samples correspond to HMECs shortly after shP53 transduction (R2shP53_Early) and several weeks after shP53 transduction (R2shP53_Late). HMECs transduced with oncogenes (either HRASV12, WNT1 or CCNE1) are named R2shp53-ONCOGENE_Late. Finaly, HMECs transduced with oncogenes were also grown in soft agar and are named R2shp53-ONCOGENE_SA after selection in soft agar. Less...