{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Increased Neurotrophin-3 Expression Promotes the Metastatic Growth of Breast Cancer Cells in the Brain","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/1951/56062"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Nearly 20% of breast cancer patients with non-localized disease are eventually diagnosed with brain lesions, making breast cancer a main source of metastatic brain disease in women. The process of metastasis is highly specific, though the molecular basis for breast cancer metastasis to the brain remains unclear. A novel proteomic signature associated with breast cancer brain metastasis showed an association of the expression of neurotrophin-3 (NT-3), a growth factor, with brain-targeting metastatic breast cancer cell lines. To evaluate the importance of NT-3 in the ability of brain-targeting breast cancer cell lines to grow in the brain, I knocked down NT-3 expression in brain-targeting metastatic breast cancer cells and overexpressed NT-3 in non brain-targeting metastatic breast cancer cells. The ability of the cells to grow in the brain was lost in cells lacking NT-3 expressing and the ability was gained in cells overexpressing NT-3. These findings show that NT-3 expression is necessary and sufficient to promote growth in the brain.  Currently, breast cancer surface receptors define the prognosis of breast cancer metastasis to the brain. Here, I show expression levels of human epidermal growth factor receptor (HER-2), a marker associated with breast cancer brain metastasis, correlate with levels of NT-3. Treatment of brain-targeting metastatic breast cancer cells with exogenous NT-3 causes activation of HER-2. This shows crosstalk between NT-3 and HER-2, suggesting a mechanism by which NT-3 can promote growth of brain metastatic breast cancer cells. Further findings elucidate a possible role between NT-3 expression by brain metastatic breast cancer cells and the microenvironment. Clinically, breast cancer brain metastases have been shown to recruit microglia, an immune cell of the brain. I show here that microglia activation is lower in the presence of tumors expressing NT-3, while breast cancer with low levels of NT-3 have high levels of activation. I propose that NT-3 can promote growth of metastatic breast cancer cells in the brain through HER-2 activation and via an interaction with the brain microenvironment."},{"label":"dcterms.available","value":"2015-04-24T14:44:45Z"},{"label":"dcterms.contributor","value":"Howard  Crawford"},{"label":"dcterms.creator","value":"Louie, Elizabeth Angela"},{"label":"dcterms.dateAccepted","value":"2012-05-17T12:21:24Z"},{"label":"dcterms.dateSubmitted","value":"2015-04-24T14:44:45Z"},{"label":"dcterms.description","value":"Department of Molecular and Cellular Pharmacology"},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/1951/56062"},{"label":"dcterms.issued","value":"2011-08-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2015-04-24T14:44:45Z (GMT). No. of bitstreams: 0\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Molecular biology -- Oncology"},{"label":"dcterms.title","value":"Increased Neurotrophin-3 Expression Promotes the Metastatic Growth of Breast Cancer Cells in the Brain"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/10%2F14%2F62%2F101462409498690145738245305350927722434/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/10%2F14%2F62%2F101462409498690145738245305350927722434","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}