PI 3-Kinase and the Histone Methyl-Transferase KMT2D Collaborate to Induce Arp2/3-Dependent Migration of Mammary Epithelial Cells.

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however, how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A.

Inactivation of PTEN and ZFHX3 in Mammary Epithelial Cells Alters Patterns of Collective Cell Migration.

Whole exome sequencing of invasive mammary carcinomas revealed the association of mutations in and tumor suppressor genes (TSGs). We generated single and combined and knock-outs (KOs) in the immortalized mammary epithelial cell line MCF10A to study the role of these genes and their potential synergy in migration regulation. Inactivation of , but not , induced the formation of large colonies in soft agar.

Insights into the Link between the Organization of DNA Replication and the Mutational Landscape.

The generation of a complete and accurate copy of the genetic material during each cell cycle is integral to cell growth and proliferation. However, genetic diversity is essential for adaptation and evolution, and the process of DNA replication is a fundamental source of mutations. Genome alterations do not accumulate randomly, with variations in the types and frequencies of mutations that arise in different genomic regions.