Research

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Regulation of the TATA-Binding Protein (TBP) by the Epidermal Growth Factor Receptor Family. 

      My current project focuses on the transcriptional regulation of a eukaryotic transcription factor, TBP. TBP is necessary for the transcription of RNA polymerase I, II and III dependent genes and was once thought of as a housekeeping gene. Recent studies by our laboratory show that increases in the expression TBP can promote cellular transformation and oncogenesis (Johnson et al., 2003). 

      Members of the epidermal growth factor receptor (EGFR) family also play a key role in many human cancers. The family members most prevalent in cancer are EGFR1 and HER2. The HER2 gene is amplified in 40% of human breast tumors and the EGFR1 gene is amplified and rearranged in human breast, brain, lung and ovarian tumors. The most common rearrangement of the EGFR1 gene is the type III variant, EGFRvIII. This mutant receptor is only expressed in tumor cells and may provide a selective growth advantage by regulating the expression of specific proteins. Our lab recently showed that TBP expression is regulated by EGF-mediated activation of EGFR1 (Zhong et al, 2004). However, regulation of TBP expression by EGFRvIII and HER2 has not been studied.

      The focus of my studies are to delineate the specific role of EGFR1, EGFRvIII and HER2 in regulating the expression of TBP. The signal transduction pathways and the transcriptional regulatory elements involved are an important aspect of these studies. The majority of these studies take advantage of an EGFR-null cell line, NR6 and engineered NR6 cell lines expressing EGFR1, EGFRvIII (Batra et al., 1995) or HER2 (Chazin et al., 1992) at levels comparable to those found in human tumors. As aberrant expression of these receptors is a prominent component in cancer, dissecting the downstream signaling events regulating TBP expression is important for understanding how these receptors contribute to oncogenesis.