Poly-ADP-Ribosylation of Estrogen Receptor-Alpha by PARP1 Mediates Antiestrogen Resistance in Human Breast Cancer Cells.

ABSTRACT: Therapeutic targeting of estrogen receptor-α (ERα) by the anti-estrogen tamoxifen is standard of care for premenopausal breast cancer patients and remains a key component of treatment strategies for postmenopausal patients. While tamoxifen significantly increases overall survival, tamoxifen resistance remains a major limitation despite continued expression of ERα in resistant tumors. Previous reports have described increased oxidative stress in tamoxifen resistant versus sensitive breast cancer and a role for PARP1 in mediating oxidative damage repair. We hypothesized that PARP1 activity mediated tamoxifen resistance in ERα-positive breast cancer and that combining the antiestrogen tamoxifen with a PARP1 inhibitor (PARPi) would sensitize tamoxifen resistant cells to tamoxifen therapy. In t

SUBMITTER: Pulliam N 

PROVIDER: S-EPMC6357000 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature