Regulation of estrogen receptor signaling in patient-derived breast cancer cultures
November 2021
University of Helsinki, Helsinki, Finland
Breast cancer is globally the most frequent cancer and the leading cause of women’s death. Two-thirds of breast cancers express the estrogen receptor (ER)-positive phenotype. ER-positive tumors have been almost impossible to grow in culture since ER protein is quickly downregulated in vitro. 400 patient-derived breast epithelial and breast cancer explant cultures were grown in various three-dimensional matrix scaffolds, finding that ER is primarily regulated by matrix stiffness. Compression of the cultures with physical force can turn on ER expression in cultured human breast cells. In addition, tumor stiffness, as indicated by mammographic density, is directly correlated to ER expression in breast cancer patients. These findings reveal a mechanobiological component in breast tissue hormonal signalling and enable the development of novel therapeutic interventions.
Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer
Juha Klefström
Added on: 10-24-2022
[1] https://www.nature.com/articles/s41467-021-27220-9#Sec12
