Molecular Determinants and Clinical Implications of Breast Cancer Dormancy.

摘要

During the first year of this project, we have made significant progress in our proposed work. We developed and tested two cell models to induce cancer dormancy: metabolic stress and Petaka incubation. We found that metabolic stress enriched quiescence population but caused spontaneous DNA breaks. Given that the goal of this project is to determine if and how DNA damage repairs play a critical role in dormancy state, metabolic stress-induced dormancy appears not to be appropriate for our study. In Petaka-induced dormancy, we found that cell dormancy facilitated DNA damage repair when cells were pre-treated with DNA damage agents, and promoted transformation phenotype and drug resistance after exited from dormant state. These observations are consistent with the fact that recurrent breast cancers are usually more malignant and more resistant to original therapy. Finally, we applied microarray analysis in cells before dormancy, maintaining in dormancy, and exited from dormancy. Further analysis of these expression profiles will help us to identify the key molecular determinants that control dormancy at different stages.