This research seeks to elucidate the molecular mechanisms underlying the regulation of specific gene expression by epidermal growth factor (EGF). These genes are VL30 genes, a class of retrovirus-like mobile genetic elements, and Beta and Gamma actin genes which encode the major cytoskeletal forms of actin. Previous studies have shown that RNA transcripts of these genes are rapidly and specifically induced following stimulation of quiescent AKR-2B cells with EGF. Available evidence suggests that specific DNA regulatory sequences are required. In addition, our data suggest a model for actin gene regulation which involves a specific protein repressor of actin gene transcription. The object of the proposed experiments are to elucidate specific DNA sequences required for the EGF-dependent regulation of VL30 and cytoskeletal actin genes and to further characterize the nature of the proposed repressor and its mode of interaction. These studies will involve the linkage of suspected VL30 and actin gene regulatory sequences to an easily monitored heterologous gene. These fusion genes will be introduced into highly EGF-responsive cells and the EGF-dependence of their expression determined. Appropriate deletion mapping techniques will be utilized to identify specific regulatory sequences and to relate them to specific regulatory functions. These studies will further our understanding of cellular growth control by peptide growth factors and may facilitate the identification of specific lesions in these mechanisms with characterize neoplastically transformed cells.
| Elder, P K; French, C L; Subramaniam, M et al. (1988) Evidence that the functional beta-actin gene is single copy in most mice and is associated with 5' sequences capable of conferring serum- and cycloheximide-dependent regulation. Mol Cell Biol 8:480-5 |
| Blatti, S P; Foster, D N; Ranganathan, G et al. (1988) Induction of fibronectin gene transcription and mRNA is a primary response to growth-factor stimulation of AKR-2B cells. Proc Natl Acad Sci U S A 85:1119-23 |
