Venkatesh, Yashika (2020) Study of crosstalk between progesterone receptor signalling and cellular stress pathways in breast cancer. Master's Research Project 2, Biomolecular Sciences.
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Abstract
Macroautophagy (autophagy) is intimately linked with cell death and allows cells to elude apoptosis. This has evoked clinical trials to combine autophagy inhibitors with other drugs with the aim of increasing the likelihood of cancer cells dying. However, the molecular basis for such effects is unknown. It has been demonstrated previously that synthetic progesterone, progestin R5020 induces cellular senescence in breast cancer cells with high levels of progesterone receptor B (PRB). The ligand-activated progesterone receptor has been reported to exert influence on cancer development by manipulating the autophagy pathway. Therefore, prolonged R5020 treatment upregulates autophagy in MCF-7 human breast cancer cells via a unique interplay between progesterone receptor B (PRB) and TFEB. These findings prompt an interesting strategy to exploit the senescence in order to check if anticancer drugs induce apoptosis synergistically with progestin R5020. Herein, I report the influence of combination treatment and co-treatment of R5020 with epigenetic modifiers, ER stress inducer and cytoskeleton disrupting drugs that act synergistically to produce synthetic lethal effect on the MCF-7 cells. Together, my findings help in hypothesising the molecular mechanisms that are involved in inducing cell death and unravel the possible link between the autophagy and apoptosis processes.
| Item Type: | Thesis (Master's Research Project 2) |
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| Supervisor name: | Kok, J. |
| Degree programme: | Biomolecular Sciences |
| Thesis type: | Master's Research Project 2 |
| Language: | English |
| Date Deposited: | 06 Aug 2020 11:00 |
| Last Modified: | 06 Aug 2020 11:00 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/23011 |
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