title: B cell translocation gene 1 contributes to antisense Bcl-2-mediated apoptosis in breast cancer cells.
abstract: The antiapoptotic protein Bcl-2 is overexpressed in a majority of breast cancers, and is associated with a diminished apoptotic response and resistance to various antitumor agents. Bcl-2 inhibition is currently being explored as a possible strategy for sensitizing breast cancer cells to standard chemotherapeutic agents. Antisense Bcl-2 oligonucleotides represent one method for blocking the antiapoptotic effects of Bcl-2. In this study, we show that antisense Bcl-2 efficiently blocks Bcl-2 expression, resulting in the apoptosis of breast cancer cells. Antisense Bcl-2-mediated cytotoxicity was associated with the induction of the B cell translocation gene 1 (BTG1). Importantly, knockdown of BTG1 reduced antisense Bcl-2-mediated cytotoxicity in breast cancer cells. Furthermore, BTG1 expression seems to be negatively regulated by Bcl-2, and exogenous expression of BTG1 induced apoptosis. These results suggest that BTG1 is a Bcl-2-regulated mediator of apoptosis in breast cancer cells, and that its induction contributes to antisense Bcl-2-mediated cytotoxic effects.
authors.affiliation: Department of Breast Medical Oncology, Unit 1354, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA. rnahta@mdanderson.org
authors.forename: Rita
authors.initials: R
authors.lastname: Nahta
authors.forename: Linda X H
authors.initials: LX
authors.lastname: Yuan
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Fiterman
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; C074086:BTG1 protein, human