Treatment Induced Autophagy Associated with Tumor Dormancy and Relapse
Abstract
Studies were performed to identify the nature of chemotherapy (and radiation) induced autophagy in the MMC breast tumor cell line and the 4T1 breast tumor cell line, both of which are syngeneic and can be grown in immune competent mice. We found that the autophagy induced in the 4t1 cells was nonprotective in that its inhibition by pharmacological or genetic approaches failed to alter sensitivity to chemotherapy or radiation. In contrast, autophagy in the MMC cells was clearly cytoprotective. These differences may be related to the p53 status of the tumor cells, as the 4T1 cells are p53 null while the MMC cells are wild-type in p53.It is generally perceived that interference with autophagy will enhance sensitivity to chemotherapy and radiation; however, this premise applies solely when the autophagy is protective. Sine mutations inp53 are common in breast cancer as well as other malignancies, having a p53 null cell line may be more relevant to clinical breast cancer than ap53 wt line.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2016
- Accession Number
- AD1019633
Entities
People
- David A. Gewirtz
Organizations
- Virginia Commonwealth University