Oncogene Dependence and Survival of Residual Cells
12/03/2013 - Room M203 at 14:00 - Pink Seminar
In patients with certain cancers interference with the activity of cancer-initiating oncogenes can result in tumor regression. However, targeted therapies are only partly successful, since relapses often occur in the presence of therapeutic agents. This problem has provoked interest in experimental models for the systematic study of oncogene dependence.
Transgenic mice carrying regulatable oncogenes allow to mimick treatment with an ideally targeted drug and represent tractable systems for studying oncogene dependence and tumor recurrence. However, since animal studies are often too complex to reveal detailed mechanistic insights, we developed a three-dimensional (3D) culture system of primary mouse mammary epithelial cells. This 3D approach recapitulated overall changes in the phenotype observed in the mammary glands of the transgenic mice from which the cultures are derived and revealed a pure population of cells that have survived oncogene withdrawal.
Preliminary results show that cells which are specified to later survive oncogene withdrawal can be distinguished from the bulk of tumor cells. Moreover, the 3D conditions allowed to obtain a distinct molecular signature that describes the special status of the surviving, dormant cells as compared to normal mammary cells. I will discuss initially identified candidate pathways and proposed mechanisms important for survival of residual cells and re-establishment of tumor relapse.