Runx1 Function in Mouse Skin Tumor Formation
| dc.contributor.author | Hoi, Charlene | |
| dc.date.accessioned | 2010-08-14T18:29:07Z | |
| dc.date.available | 2010-08-14T18:29:07Z | |
| dc.date.issued | 2010-08-14T18:29:07Z | |
| dc.description.abstract | Adult stem cells, which are characterized by their slow-cycling, multi-potent and self-renewing nature, are crucial in maintaining tissue homeostasis and responding to wound-stimuli. In addition to these classical roles, one current hypothesis posits that deregulated adult stem cells may in fact be the origin of cancer-initiating cells. Within the epidermis, hair follicle stem cells (HFSCs) give rise to and maintain the hair follicle structure through a series of remodeling phases known as ‘hair cycles’. The transcription factor Runx1, also known as AML1, plays a role in the activation of HFSCs by prolonging the quiescent phase of the hair cycle when ablated. Coincidently, Runx1 is also translocated in 20-30% of patients afflicted with the blood-related disease acute myeloid leukemia. In this study, we explore the role that Runx1 may have in skin tumorigenesis by using a mutagen (9,10-Dimethyl-1,2-benzanthracene, DMBA) and a phorbol ester mitogen (12-O-tetradecanoylphorbol-13-acetate, TPA) in a two-step, oncogenic protocol. First, we observe that epithelial-specific Runx1-mutant mice show decreased levels of phosphorylated Stat3 and acquire significantly fewer papillomas than their wild-type littermates in response to carcinogenic drug treatment, a phenotype which is reversed when the cell cycle regulator p21 is simultaneously knocked-out. Second, cells initially expressing Runx1 contribute to tumor formation. Lastly, induced removal of functional Runx1, which is up-regulated in tumors, following tumor formation actually resulted in a reduction in overall tumor volume. Taken all together, these results suggest that Runx1 functions upstream of p21 and is involved in not only the initiation of tumors, but also their proliferation and progression, possibly via the Jak/Stat pathway | en_US |
| dc.identifier.uri | https://hdl.handle.net/1813/17311 | |
| dc.language.iso | en_US | en_US |
| dc.title | Runx1 Function in Mouse Skin Tumor Formation | en_US |
| dc.type | dissertation or thesis | en_US |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- Hoi, Charlene.pdf
- Size:
- 10.51 MB
- Format:
- Adobe Portable Document Format
- Description: