Forced expression of Oct4 dysregulates the LIF-mediated monocytic differentiation of mouse M1 leukemia cells .
碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 98 === Abstract M1 leukemia cell line is a well established cell model to study myeloid cell differentiation as they undergo monocytic differentiation with growth arrest and apoptosis when stimulated with Leukemia Inhibitory Factor (LIF) or Interleukin-6 (IL-6). It h...
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| Format: | Others |
| Language: | zh-TW |
| Published: |
2010
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| Online Access: | http://ndltd.ncl.edu.tw/handle/02268229920847719760 |
| Summary: | 碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 98 === Abstract
M1 leukemia cell line is a well established cell model to study myeloid cell differentiation as they undergo monocytic differentiation with growth arrest and apoptosis when stimulated with Leukemia Inhibitory Factor (LIF) or Interleukin-6 (IL-6). It has previously been shown that enforced expression of c-Myc in M1 cells blocked the LIF-mediated terminal differentiation at an intermediate stage in the progression from immature blasts to mature macrophages and Egr-1 can abrogate this block. The primary aim of this thesis is to examine the effect of over-expression of Oct4 in M1 cells on the LIF-mediated monocytic differentiation program.
We observe that enforced expression of Oct4 in M1 leukemia cells (M1.Oct4) leads to dispersed typed colony formation in semi-solid agar cultures in the absence of LIF, similar to those differentiated colonies found in the agar cultures of M1 or M1.GFP cells stimulated with LIF. The M1.Oct4 cells have reduced expression of a monocytic marker - CD11b / Mac-1 antigen when compared to the parental M1 and M1.GFP control cells. Furthermore exposure of the M1.Oct4 cells to LIF results in suppression of cell proliferation and extensive cell death which is coupled with an early loss of clonogenic cells and onset of programmed cell death, when compared with the M1 or M1.GFP control cells. Lastly forced expression of Oct4 in M1 cell does not completely block the LIF-mediated terminal monocytic differentiation.
In conclusion, forced expression of Oct4 dysregulates the LIF- mediated monocytic differentiation of mouse M1 leukemia cells. These observations highlight a new perspective in the differential role played by Oct4 in M1 leukemia and pluripotent ES cells.
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