Role of Prolactin in a Preclinical Model of Breast Cancer Mediated Osteolysis.
| dc.contributor.advisor | Shemanko, Carrie S. | |
| dc.contributor.author | Gopinathan, Sesha Gopal | |
| dc.contributor.committeemember | Moorhead, Greg B. G. | |
| dc.contributor.committeemember | Hollenberg, Morley Donald | |
| dc.date | 2019-11 | |
| dc.date.accessioned | 2019-09-03T18:51:05Z | |
| dc.date.available | 2019-09-03T18:51:05Z | |
| dc.date.issued | 2019-08-29 | |
| dc.description.abstract | At the advanced stage, breast cancer metastasizes to the bone and initiates the vicious cycle of cancer by actively inducing osteoclast differentiation which causes excessive bone degradation. Prolactin (PRL) is a hormone involved in key functions such as mammary gland development and bone homeostasis. We demonstrated that PRL also stimulates breast cancer mediated osteoclastogenesis. The overall goal of my project is to study the role of PRL in breast cancer mediated bone degradation using mouse models. The breast cancer cells chosen for this study were engineered to emit bioluminescence and secrete PRL (MCF7-BGL hPRL) or not (MCF7-BGL-EV). During cell line characterization, MCF7-BGL-hPRL cells demonstrated better osteoclast differentiation via TRAP+ staining, indicating osteolysis potential. Using western blots, the level of PRL secreted by MCF7-BGL-hPRL and the presence of long isoform of PRLR on both the cell lines were quantified. Further, a slight fold difference in the bioluminescence signal intensity between these two cell line was identified and taken into consideration for in vivo experiments. Simultaneously, the role of PRL in osteoblast differentiation and its facilitation of osteoclast differentiation was studied and it showed no influence. Mouse tibia injected with MCF7-BGL-hPRL and MCF7-BGL-EV cells respectively achieved bioluminescence endpoint at 3 weeks and the microCT analysis at 6 weeks revealed higher bone damage in MCF7-BGL-hPRL injected tibia compared to the MCF7-BGL-EV injected tibia. However, a second experiment where the BLI endpoint reached only at 6 weeks showed relatively less bone loss for the same time point. The cumulative results from both the experiments show significant loss in bone mineral density and difference in trabecular thickness in MCF7-BGL-hPRL injected and its uninjected control tibiae, but no difference was observed between the two cell lines. This in vivo study of PRL induced breast cancer mediated osteolysis was never performed before and the valuable information learned from my study outcome sets a platform for future studies. | en_US |
| dc.identifier.citation | Gopinathan, S. G. (2019). Role of Prolactin in a Preclinical Model of Breast Cancer Mediated Osteolysis (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/36925 | |
| dc.identifier.uri | http://hdl.handle.net/1880/110847 | |
| dc.language.iso | eng | en_US |
| dc.publisher.faculty | Science | en_US |
| dc.publisher.institution | University of Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | en_US |
| dc.subject | Breast Cancer | en_US |
| dc.subject | Bone metastasis | en_US |
| dc.subject.classification | Education--Sciences | en_US |
| dc.subject.classification | Biology--Cell | en_US |
| dc.title | Role of Prolactin in a Preclinical Model of Breast Cancer Mediated Osteolysis. | en_US |
| dc.type | master thesis | en_US |
| thesis.degree.discipline | Biological Sciences | en_US |
| thesis.degree.grantor | University of Calgary | en_US |
| thesis.degree.name | Master of Science (MSc) | en_US |
| ucalgary.item.requestcopy | true | en_US |