Show simple item record

dc.contributor.authorMcGrath, Julie Elaine
dc.date.accessioned2016-04-05T19:59:38Z
dc.date.available2016-04-05T19:59:38Z
dc.date.issued2015
dc.identifier.isbn9781339104348
dc.identifier.other1723352435
dc.identifier.urihttp://hdl.handle.net/10477/51641
dc.description.abstractBreast cancer cell dormancy is a significant clinical problem which contributes to the development of distant metastasis and disease relapse. Currently, no therapies exist which can effectively detect or eradicate dormant cancer cells. In this study, we utilized a 3D co-culture dormancy model, recapitulating the inhibitory hematopoietic stem cell niche, which interacts with MDA-MB-231 cells, causing them to enter a state of growth arrest. The knockdown of emerging dormancy regulator gene, p38/MAPK14, in MDA-MB-231 cells allows previously dormant cells to "break" dormancy and re-enter the cell cycle when grown in the inhibitory niche. Using the newly described in vitro dormancy model, we performed a genomic shRNA library screen, and identified several p38-regulated breast cancer dormancy suppressor gene candidates. Two p38-regulated gene candidates were investigated further. Knockdown of transcription factors and p38 substrates, HBP1 and BHLHB3, in MDA-MB-231 cells lead to re-activation (proliferation) of once indolent cells when cultured in the inhibitory niche. The present study illustrates the role of p38 and p38-regulated genes in breast cancer dormancy within the microenvironment of the inhibitory (endosteal) hematopoietic stem cell niche. Additionally, we have identified a list of ~700 breast cancer dormancy suppressor candidate genes. Further analysis and validation experiments are needed to classify novel molecular players and signaling pathways involved in tumor cell dormancy from the list of candidate genes generated in this study.
dc.languageEnglish
dc.sourceDissertations & Theses @ SUNY Buffalo,ProQuest Dissertations & Theses Global
dc.subjectBiological sciences
dc.subjectBreast cancer
dc.subjectDormancy
dc.subjectHematapoetic niche
dc.subjectMetastasis
dc.subjectGenetic screening
dc.subjectshRNA
dc.titleGenetic Screen Identifies Candidate Breast Cancer Tumor Dormancy Suppressor Genes Using Cellecta's Decipher Pooled shRNA Libraries
dc.typeDissertation/Thesis


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record