Accession Number : AD1019633


Title :   Treatment Induced Autophagy Associated with Tumor Dormancy and Relapse


Descriptive Note : Technical Report,01 Jul 2015,30 Jun 2016


Corporate Author : Virginia Commonwealth University Richmond United States


Personal Author(s) : Gewirtz,David A


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1019633.pdf


Report Date : 01 Jul 2016


Pagination or Media Count : 17


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.


Descriptors :   breast cancer , tumor cell line , neoplasms , chemotherapy , immunotherapy , biological aging


Distribution Statement : APPROVED FOR PUBLIC RELEASE