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ROLE OF DEAF-1 IN TRANSCRIPTIONAL REGULATION OF PTEN AND EFFECTS OF DEAF-1 OVEREXPRESSION IN HUMAN RHABDOMYOSARCOMA CELL LINES

Deformed epidermal autoregulatory factor -1 (DEAF-1) is a transcription factor mapping to the chromosomal region 11p15.5, a region associated with loss of heterozygosity (LOH) in human cancers. Potential DEAF-1 binding motifs were identified in the PTEN promoter and the ability of DEAF-1 to regulate PTEN gene expression was investigated. DEAF-1 increased transcription 10-14 fold with PTEN sequences between -429 and -221, while mutations in the DNA binding domain (DEAF-ADWA) and nuclear localization signal of DEAF-1 abolished this increase. DEAF-1 was shown to bind sequences between -339 and -233. Rabdomyosarcoma (RD) stable cell lines with inducible expression of DEAF-1 and DEAF-1-ADWA were produced. Increased DEAF-1 expression had no significant effects on PTEN RNA expression or cell proliferation when compared to controls, but did increase susceptibility to UV-induced apoptosis. These studies suggest that DEAF-1 may contribute to the regulation of PTEN gene expression, but other factors may play a more significant role.

Identiferoai:union.ndltd.org:siu.edu/oai:opensiuc.lib.siu.edu:theses-1980
Date01 December 2012
CreatorsKhan, Saira
PublisherOpenSIUC
Source SetsSouthern Illinois University Carbondale
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses

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