Cancer has been a disease, which has generated intense research interest for many years. Misexpression of two oncoproteins, TAL 1 and LMO 1, has been found to help induce a particular type of leukemia, called T-cell acute lymphoblastic leukemia (T-ALL). Presently, it is not completely understood how these proteins induce leukemogenesis or what other cellular proteins they interact with to drive this progression. In this study, a series of experiments were conducted to identify downstream targets of TALI and LMO1. Using retroviral gene transfer, both genes were introduced, either singly or in combination, into a murine T-cell line called AKR-DP-603. Empty vectors were introduced as controls. In order to assay the effects of TALI and LMO I expression on expression of other proteins, a series of Western blots were completed on all populations of engineered cells. It was determined that there were differences in expression of Bcl-2 and p16 as indicated by differences in band intensities on the blots. This is important because it implies an effect on protein levels by TAL 1 and LMO 1. However, there were no differences in protein expression levels for Bax or cyclin D1. This suggests that TAL1 and LMOI do not have any regulatory effects on these proteins. In addition, apoptotic assays were completed on all populations of cells. The results of both a TUNEL assay and ethidium bromide/acridine orange staining protocol showed TAL1- and LMO1expressing cells to have an increase in cell survival under starvation conditions and a lower frequency of apoptosis. Statistical analysis verified significant difference in the apoptosis assays. The data suggests an up-regulation of anti-apoptotic proteins. The finding of this research allow a clearer understanding of the process of leukemogenesis and may lead to a development of better cancer treatments. / Department of Biology
| Identifer | oai:union.ndltd.org:BSU/oai:cardinalscholar.bsu.edu:handle/187041 |
| Date | January 2001 |
| Creators | Fettig, Amy E. |
| Contributors | Olesen, James B. |
| Source Sets | Ball State University |
| Detected Language | English |
| Format | ii, 65 leaves : ill., charts ; 28 cm. |
| Source | Virtual Press |
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