Differential response to exercise in claudin-low breast cancer.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Glass, OK; Bowie, M; Fuller, J; Darr, D; Usary, J; Boss, K; Choudhury, KR; Liu, X; Zhang, Z; Locasale, JW; Williams, C; Dewhirst, MW; Jones, LW; Seewaldt, V

Published Date

  • November 24, 2017

Published In

Volume / Issue

  • 8 / 60

Start / End Page

  • 100989 - 101004

PubMed ID

  • 29254140

Pubmed Central ID

  • 29254140

Electronic International Standard Serial Number (EISSN)

  • 1949-2553

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.21054


  • eng

Conference Location

  • United States