From Breast to Bone: Tracking Gene Expression Changes Responsible for Breast Cancer Metastasis in a Humanized Mouse Model with Molecular Imaging
Technical Report,01 Sep 2011,31 Aug 2015
The University of Texas MD Anderson Cancer Center Houston United States
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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 idetermine 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.