Research Papers:
Differential response to exercise in claudinlow breast cancer
PDF | Full Text | Supplementary Files | How to cite
Metrics: PDF 2531 views | Full Text 4455 views
Oliver K. Glass1, Michelle Bowie1, Julie Fuller1, David Darr2, Jerry Usary3, Keara Boss4, Kingshuk Roy Choudhury1, Xioajing Liu1, Zoe Zhang1, Jason W. Locasale1, Christina Williams1, Mark W. Dewhirst1,*, Lee W. Jones5,6,* and Victoria Seewaldt7,*
1 Duke University Medical Center, Durham, NC, USA
2 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
3 Arrow Genomics LLC, Chapel Hill, NC, USA
4 North Carolina State University, Raleigh, NC, USA
5 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
6 Weill Cornell Medical College, New York, NY, USA
7 City of Hope Cancer Center, Duarte, CA, USA
* These authors have contributed equally to this work
Correspondence to:
Lee W. Jones, email:
Mark W. Dewhirst, email:
Keywords: exercise, breast cancer, Hif1-α, mouse model, claudin-low
Received: July 18, 2017 Accepted: August 23, 2017 Published: September 19, 2017
Abstract
Exposure to exercise following a breast cancer diagnosis is associated with reductions in the risk of recurrence. However, it is not known whether breast cancers within the same molecular-intrinsic subtype respond differently to exercise. Syngeneic mouse models of claudin-low breast cancer (i.e., EO771, 4TO7, and C3(1)SV40Tag-p16-luc) were allocated to a uniform endurance exercise treatment dose (forced treadmill exercise) or sham-exercise (stationary treadmill). Compared to sham-controls, endurance exercise treatment differentially affected tumor growth rate: 1- slowed (EO771), 2- accelerated (C3(1)SV40Tag-p16-luc), or 3- was not affected (4TO7). Differential sensitivity of the three tumor lines to exercise was paralleled by effects on intratumoral Ki-67, Hif1-α, and metabolic programming. Inhibition of Hif1-α synthesis by the cardiac glycoside, digoxin, completely abrogated exercise-accelerated tumor growth in C3(1)SV40Tag-p16-luc. These results suggest that intratumoral Hif1-α expression is an important determinant of claudin-low breast cancer adaptation to exercise treatment.