title: Breast cancer-amplified sequence 3, a target of metastasis-associated protein 1, contributes to tamoxifen resistance in premenopausal patients with breast cancer.
abstract: Lysine acetylation occurs in many protein targets, including core histones, transcription factors, and other proteins. Metastasis-associated protein 1 (MTA1) is implicated in the progression and metastasis of various epithelial tumors. Because MTA1 functions as a transcriptional coregulator, much of its role in cancer promoting processes are likely to involve its ability to regulate the transcription of downstream target genes that encode effector proteins. We recently showed that MTA1 could be post-translationally modified by acetylation, which modulates its function as a coregulator molecule. We also defined a chromatin target of MTA1, namely, breast cancer-amplified sequence 3 (BCAS3), in the context of which MTA1 behaves as a transcriptional coactivator in breast cancer cells. Because the phenotypic effect of BCAS3 overexpression in tumors has not been defined, we investigated the consequence of increased expression of BCAS3 in human breast tumors. Here, we report that BCAS3 overexpression in hormone receptor-positive premenopausal breast cancer seemed to be associated with impaired responses to tamoxifen. Our findings have implications for endocrine therapy.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Anupama E
authors.initials: AE
authors.lastname: Gururaj
authors.forename: Caroline
authors.initials: C
authors.lastname: Holm
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000107:Acetylation; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017697:Premenopause; D012097:Repressor Proteins / Q000378:metabolism*; D015996:Survival Rate; D013629:Tamoxifen / Q000494:pharmacology*; D015534:Trans-Activators
chemical_list: C470217:BCAS3 protein, human; C089320:MTA1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D013629:Tamoxifen; D006655:Histone Deacetylases