Histone deacetylase (
HDAC) proteins, which regulate the acetylation state of
proteins, are the targets of multiple clinical drugs for
cancer treatment. Due to the heterogeneity of
tumors,
HDAC proteins play different roles in the progression of various
cancer types. For example, MDA-MB-468 and MDA-MB-231 cells are both
triple negative breast cancer cells but belong to different subtypes that display different response to
HDAC inhibitor drugs. To investigate the role of
HDAC proteins in
breast cancer, the substrate and associated
proteins of HDAC1 in MDA-MB-231, MDA-MB-468, and a normal breast epithelial cell line, MCF10A, were analyzed using substrate trapping mutants and proteomics-based mass spectrometry. All three cell lines demonstrated nonoverlapping substrate
protein profiles. While both normal MCF10A and cancerous MDA-MB-468 cell lines contained similar HDAC1 associated
proteins, including
proteins associated with epigenetic and RNA processing mechanisms, the HDAC1 associated
protein profile of MDA-MB-231 cells was devoid of expected epigenetic
proteins. The variable associated
protein profiles of MDA-MB-231 and MDA-MB-468 suggest that HDAC1 plays distinct roles in
breast cancer cell biology, which might affect
cancer aggressiveness and
HDAC inhibitor sensitivity.