| dc.identifier.uri | http://hdl.handle.net/1951/56062 | |
| dc.identifier.uri | http://hdl.handle.net/11401/70814 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | 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. | |
| dcterms.available | 2012-05-17T12:21:24Z | |
| dcterms.available | 2015-04-24T14:44:45Z | |
| dcterms.contributor | Howard Crawford | en_US |
| dcterms.contributor | Emily Chen. Styliani-Anna Tsirka. | en_US |
| dcterms.contributor | Mary Kritzer. | en_US |
| dcterms.creator | Louie, Elizabeth Angela | |
| dcterms.dateAccepted | 2012-05-17T12:21:24Z | |
| dcterms.dateAccepted | 2015-04-24T14:44:45Z | |
| dcterms.dateSubmitted | 2012-05-17T12:21:24Z | |
| dcterms.dateSubmitted | 2015-04-24T14:44:45Z | |
| dcterms.description | Department of Molecular and Cellular Pharmacology | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/1951/56062 | |
| dcterms.identifier | Louie_grad.sunysb_0771E_10657.pdf | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/70814 | |
| dcterms.issued | 2011-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2012-05-17T12:21:24Z (GMT). No. of bitstreams: 1
Louie_grad.sunysb_0771E_10657.pdf: 38412853 bytes, checksum: 11469b03011a2bc1289056a64acd2841 (MD5)
Previous issue date: 1 | en |
| dcterms.provenance | Made available in DSpace on 2015-04-24T14:44:45Z (GMT). No. of bitstreams: 0
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Molecular biology -- Oncology | |
| dcterms.subject | Brain metastasis, Breast cancer, Microglia, Neurotrophin-3 | |
| dcterms.title | Increased Neurotrophin-3 Expression Promotes the Metastatic Growth of Breast Cancer Cells in the Brain | |
| dcterms.type | Dissertation | |
