Accession Number : ADA301625

Title :   Identification of Novel Candidate Tumor Suppressor Genes Using C. Elegans as a Model.

Descriptive Note : Annual rept. 1 Nov 94-31 Oct 95,

Corporate Author : CALIFORNIA INST OF TECH PASADENA

Personal Author(s) : Sternberg, Paul W.

PDF Url : ADA301625

Report Date : 29 SEP 1995

Pagination or Media Count : 28

Abstract : Molecular and genetic analysis in the model organism Caenorhabditis elegans was used to identify new negative regulators of tyrosine kinase/ras mediated signal transduction pathways that are candidate tumor suppressors. A nematode homolog of the cbl proto-oncogene was shown to act by regulating activation of Ras by an epidermal growth factor receptor homolog (LET-23). The rok-1 (regulator of kinase-mediated signaling) locus of C. elegans was molecularly cloned by correlating genetic and physical maps and rescue of mutant phenotypes in transgenic nematodes. A new locus, rok-2 was identified in a genetic screen for mutations that hyperactivate the LET-23 signaling pathway in the absence of SLI-1 function. Genetic interactions among these nematode negative regulatory mutations were examined by the construction of multiple mutant strains; these results suggest that multiple pathways regulate the tyrosine kinase/ras signal transduction. These results will help elucidate the function of the cbl family of proto- oncogenes, and to identify novel candidate tumor suppressor loci.

Descriptors :   *NEOPLASMS, *GENES, *GENETICS, *CANCER, *SUPPRESSORS, *BREAST CANCER, ACTIVATION, INTERACTIONS, MOLECULES, PHYSICAL PROPERTIES, MUTATIONS, REGULATORS, SIGNALS, STRAINS(BIOLOGY), MAPS, CLONES, TRANSDUCERS, LOCUS.

Subject Categories : Anatomy and Physiology
      Genetic Engineering and Molecular Biology

Distribution Statement : APPROVED FOR PUBLIC RELEASE