Accession Number : AD1006298


Title :   From Breast to Bone: Tracking Gene Expression Changes Responsible for Breast Cancer Metastasis in a Humanized Mouse Model with Molecular Imaging


Descriptive Note : Technical Report,01 Sep 2011,31 Aug 2015


Corporate Author : The University of Texas MD Anderson Cancer Center Houston United States


Personal Author(s) : Powell,Emily C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1006298.pdf


Report Date : 01 Nov 2015


Pagination or Media Count : 37


Abstract : Breast cancer is the leading cause of cancer-related death in women worldwide, and metastasis is responsible for the majority of these deaths. Triple-negative breast cancer (TNBC) is an aggressively metastatic subtype exhibiting a disproportionate degree of TP53 mutation compared with other breast cancer subtypes. The major goals of the studies described here were to (i)determine how p53 loss contributes to the metastatic potential of breast cancer cells; (ii) identify transcriptional changes that enhance breast cancer metastasis to the lungs; (iii) functionally characterize how these changes contribute to breast cancer metastasis; and (iv) validate our findings in human breast cancer samples. We used tumor models of metastatic TNBC that differed only in p53 status to characterize the effect of p53 loss in various stages of metastasis. We isolated metastatic tumor subpopulations from lungs and passaged them in vivo to enrich for metastasis. The isolation and transcriptional profiling of primary and metastatic subpopulations allowed the identification of genes that are differentially expressed between primary tumors and metastatic lesions. A subset of these genes is currently being functionally validated in gain-of-function in vivo screens. These studies are expected to stimulate the development of therapeutic strategies to predict and prevent metastasis.


Descriptors :   breast cancer , metastasis , models , gene expression , neoplasms , therapeutics , DIAGNOSTIC IMAGING


Distribution Statement : APPROVED FOR PUBLIC RELEASE