title: Ubiquitous Brms1 expression is critical for mammary carcinoma metastasis suppression via promotion of apoptosis.
abstract: Morbidity and mortality of breast cancer patients are drastically increased when primary tumor cells are able to spread to distant sites and proliferate to become secondary lesions. Effective treatment of metastatic disease has been limited; therefore, an increased molecular understanding to identify biomarkers and therapeutic targets is needed. Breast cancer metastasis suppressor 1 (BRMS1) suppresses development of pulmonary metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Little is known of Brms1 function throughout the initiation and progression of mammary carcinoma. The goal of this study was to investigate mechanisms of Brms1-mediated metastasis suppression in transgenic mice that express Brms1 using polyoma middle T oncogene-induced models. Brms1 expression did not significantly alter growth of the primary tumors. When expressed ubiquitously using a β-actin promoter, Brms1 suppressed pulmonary metastasis and promoted apoptosis of tumor cells located in the lungs but not in the mammary glands. Surprisingly, selective expression of Brms1 in the mammary gland using the MMTV promoter did not significantly block metastasis nor did it promote apoptosis in the mammary glands or lung, despite MMTV-induced expression within the lungs. These results strongly suggest that cell type-specific over-expression of Brms1 is important for Brms1-mediated metastasis suppression.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, 1670 University Blvd., VH-G019, Birmingham, AL 35294, USA.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Cook
authors.forename: Xuemei
authors.initials: X
authors.lastname: Cao
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Dowell
authors.forename: Michael T
authors.initials: MT
authors.lastname: Debies
authors.forename: Mick D
authors.initials: MD
authors.lastname: Edmonds
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Beck
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kesterson
authors.forename: Renee A
authors.initials: RA
authors.lastname: Desmond
authors.forename: Andra R
authors.initials: AR
authors.lastname: Frost
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Hurst
authors.forename: Danny R
authors.initials: DR
authors.lastname: Welch
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C544679:BRMS1 protein, mouse; D012097:Repressor Proteins