The parent project for this FIRCA application proposes to identify new genes involved in cell growth control by their ability, when inactivated, to transform mouse fibroblasts. Genetic suppressor elements (GSE) are fragments of genes that encode either antisense RNA or truncated proteins acting as dominant negative mutants. The effects of these GSEs (derived from a library of randomly fragmented normalized cDNA) and resulting isolated genes can then be characterized by their effects on cultured cells. Finally, the investigators would clone the human homologs to analyze their association with cancer. The purpose of the FIRCA study is to employ the GSE approach of the parent grant and apply it to a specific gene, p53, to identify the domains of this gene that affect the specific phenotypes, anchorage dependence and response to dominant oncogenes. A proposed methodology in the parent grant, the two-hybrid system, will be applied to p53 to isolate and characterize p53 interactors. Using the GSE and two-hybrid approaches, the investigators hope to characterize new factors in the p53 pathway.
| Nikiforov, M A; Hagen, K; Ossovskaya, V S et al. (1996) p53 modulation of anchorage independent growth and experimental metastasis. Oncogene 13:1709-19 |
