Breast Cancer

ABSTRACT: Endocrine resistance in breast cancer is a major clinical problem with poorly understood mechanisms. Mass spectrometry-based proteomics of a clinically-relevant tamoxifen-resistant cell line model identified increased levels of minichromosome maintenance proteins (MCM), including MCM3, as central in cell cycle and DNA replication protein-protein interaction networks associated with tamoxifen resistance. Lowering MCM3 protein expression in tamoxifen-resistant cells restored tamoxifen sensitivity and altered phosphorylation of several cell cycle regulators, such as p53(Ser315, 33), CHK1(Ser317) and cdc25b(Ser323), suggesting that MCM3 activation of important cell cycle-associated proteins overcomes tamoxifen’s anti-proliferative effects. High MCM3 expression in primary tumor tissue from two independent cohorts of ER+ breast cancer patients receiving adjuvant tamoxifen mono-therapy was an independent prognostic marker significantly associated with a shorter recurrence-free survival.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Jens Andersen  

LAB HEAD: Henrik J. Ditzel

PROVIDER: PXD001087 | Pride | 2022-02-22

REPOSITORIES: Pride