Rhabdomyosarcoma (RMS) is a malignant soft-tissue sarcoma in children, accounting for about 40% of pediatric soft-tissue tumours. Five-year survival for metastatic RMS is only about 25%. Furthermore, there has been no significant improvement in RMS survival since 1975, pointing to a need for improved therapy.
Previous work in our lab has shown that 4-hydroxytamoxifen (4OHT) leads to increased apoptosis and decreased viability in RMS cells. Expanding on this work, the current project aims to elucidate the mechanisms behind 4OHT-induced apoptosis in RMS cells, focusing on the roles of estrogen receptors (ER) and MAP kinases (MAPK).
We found that: 1) 4OHT-induced apoptotic signaling was associated with increased MAPK phosphorylation, 2) Inhibition of MAPK protected cells against 4OHT, 3) Inhibition of ER also protected against 4OHT, and 4) ER inhibition blocked 4OHT-associated MAPK phosphorylation.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/30566 |
| Date | 06 December 2011 |
| Creators | Chen, Kevin Min |
| Contributors | Malkin, David |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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