mdm2 Amplification in NIH3T3L1 Preadipocytes Leads to Mdm2 Elevation in Terminal Adipogenesis

 
 
 
 

mdm2 Amplification in NIH3T3L1 Preadipocytes Leads to Mdm2 Elevation in Terminal Adipogenesis

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dc.contributor.advisor Berberich, Steve en_US
dc.contributor.author Litteral, Vaughn en_US
dc.date.accessioned 2009-04-10T07:54:37Z
dc.date.available 2009-04-10T07:54:37Z
dc.date.created 2008 en_US
dc.date.issued 2009-04-10T07:54:37Z
dc.identifier.uri http://rave.ohiolink.edu/etdc/view?acc_num=wright1216825497 en_US
dc.identifier.uri http://hdl.handle.net/2374.OX/107834
dc.description The p53 protein is a tumor suppressor protein that is mutated or non-functional in nearly all cancers. The Mdm2 protein has the ability to functionally inactivate p53 and these two proteins have been studied extensively in the context of cellular proliferation. In this study, expression of the murine double minute 2 (mdm2) gene was examined in the mouse NIH3T3L1 cell line. Under the proper conditions, the immortalized NIH3T3L1 cells have the ability to differentiate from fibroblasts to adipocytes (Green et al., 1975). This well characterized cell line provides an excellent model to study mdm2 in differentiation. While evaluating the regulation of the mdm2 gene during adipogenesis, it was discovered that NIH3T3L1 preadipocytes possess a 36-fold elevation of mdm2 mRNA relative to A31 cells, another Balb/c 3T3 fibroblast cell line that lacks the capacity to differentiate (Berberich et al., 1999). Based on Southern blot analysis, this increase in mdm2 mRNA is the result of a 60 fold gene amplification (Berberich et al., 1999). This study evaluated how mdm2, p53 and other associated gene products change as NIH3T3L1 cells differentiate from preadipocytes to adipocytes. Most surprising, the mdm2 mRNA and protein levels remained high throughout differentiation and Mdm2 changes localization and interaction with key proteins. This work further proves adipogenesis can occur in the presence of high levels of Mdm2 expression. Herein, Mdm2 is shown to preferentially interact with the retinoblastoma protein, pRb, in terminal adipocytes versus preadipocytes. The p53 mRNA, protein levels and DNA binding (data not shown) decreased and the results suggest that Mdm2 could have a more p53 independent role in adipogenesis. Finally, this work leads to future experiments of determining the importance of high level Mdm2 expression in terminal adipogenesis. en_US
dc.format application/pdf en_US
dc.format 89p. en_US
dc.rights unrestricted en_US
dc.rights Copyright and permissions information available at the source archive en_US
dc.subject mdm2 en_US
dc.subject mdm-2 en_US
dc.subject Rb en_US
dc.subject retinoblastoma en_US
dc.subject p53 en_US
dc.subject cancer en_US
dc.subject adipogenesis en_US
dc.subject liposarcoma en_US
dc.subject adipose en_US
dc.subject oncogene en_US
dc.subject C/EBP en_US
dc.subject tumor suppressor en_US
dc.subject NIH3T3L1 en_US
dc.subject NIH3T3-L1 en_US
dc.subject NIH3T3 en_US
dc.subject amplification en_US
dc.subject chromosomal amplification en_US
dc.subject Southern en_US
dc.subject Northern en_US
dc.subject Western en_US
dc.subject immunoprecipitation en_US
dc.subject mdm4 en_US
dc.subject mdmX en_US
dc.subject cance en_US
dc.title mdm2 Amplification in NIH3T3L1 Preadipocytes Leads to Mdm2 Elevation in Terminal Adipogenesis en_US
dc.type Electronic Thesis or Dissertation en_US
dc.degree.name MS en_US
dc.degree.level masters en_US
dc.degree.discipline Biochemistry and Molecular Biology en_US
dc.degree.grantor Wright State University en_US
dc.contributor.publisher Wright State University / OhioLINK en_US

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