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Identification of Mechanisms and Pathways Involved in MLL2-Mediated Tumorigenesis

dc.contributor.advisor He, You-Wen Chang, Chun-Chi 2013-11-14T19:16:33Z 2015-11-04T05:30:04Z 2013
dc.description.abstract <p>Myeloid/lymphoid or mixed-lineage leukemia (MLL)-family genes encode histone lysine methyltransferases that play important roles in epigenetic regulation of gene transcription, and these genes are frequently mutated in human cancers. While MLL1 and MLL4 have been the most extensively studied, MLL2 and its homolog MLL3 are not well-understood. Specifically, little is known regarding the extent of global MLL2 involvement in the regulation of gene expression and the mechanism underlying its alterations in mediating tumorigenesis. To study the role of MLL2 in tumorigenesis, we somatically knocked out MLL2 in a colorectal carcinoma cell line, HCT116. We observed that the MLL2 loss of function results in significant reduction of cell growth and multinuclear morphology. We further profiled MLL2 regulated genes and pathways by analyzing gene expression in MLL2 wild-type versus MLL2-null isogenic cell lines. Our results reveal the connection of MLL2 to multiple cellular signaling pathways and suggest potential mechanisms underlying tumorigenesis mediated by MLL2 alterations.</p>
dc.subject Oncology
dc.subject Molecular biology
dc.subject Genetics
dc.subject Colorectal Carcinoma
dc.subject MLL2
dc.subject Retinoic acid receptor signaling
dc.subject S100A
dc.subject somatic targeting
dc.title Identification of Mechanisms and Pathways Involved in MLL2-Mediated Tumorigenesis
dc.type Master's thesis
dc.department Pathology
duke.embargo.months 24

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