Abstract 4849: Role of autophagy in breast cancer metastasis and treatment

Abstract Autophagy has shown to be important for tissue homeostasis and many human diseases as well as cancer. However, in cancer its role is controversial because autophagy may both promote and inhibit tumor development and progression. In cancer treatment, autophagy may control the likelihood with which tumor cells die but for different treatments and different tumors these effects may be opposite. Breast cancer is the most common type of cancer in women in the US; and, although it is not yet clear how should we manipulate autophagy in people with cancer, autophagy is already being manipulated in breast cancer patients in clinical trials. Moreover, because most anti-cancer treatments induce autophagy, we may also be inadvertently manipulating autophagy in the majority of breast cancer patients. To evaluate if autophagy is important in breast cancer progression and treatment, we used murine 4T1 cells, a model of metastatic breast cancer. Using matched tumor cells with different metastatic potential we found that basal autophagy was increased with increasing metastasis implying that autophagy is required to allow metastatic progression. To test if treatments that are used for metastatic breast cancer were affected by autophagy, we examined LC3 processing after 4T1 cell treatment with common breast cancer treatments including etoposide, cisplatin, doxorubicin and cyclophosphamide. In all cases, these drugs increased autophagy; however, although autophagy inhibition with chloroquine treatment increased cell death in clonogenic assays, Atg12 knockdown in 4T1 cells had no effect on either long or short term viability assays after treatment with the four chemotherapeutic drugs. Thus, we hypothesize that inhibition of specific steps in the autophagic pathway might have different effects on cell viability after treatment. Further testing of this hypothesis will be discussed. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4849.