Accession Number : ADA321228

Title :   Amplified Genes in Breast Cancer: Molecular Targets for Investigation and Therapy.

Descriptive Note : Annual rept. 1 Sep 95-31 Aug 96,

Corporate Author : SALK INST FOR BIOLOGICAL STUDIES LA JOLLA CA

Personal Author(s) : Wahl, Geoffrey M.

PDF Url : ADA321228

Report Date : SEP 1996

Pagination or Media Count : 16

Abstract : We previously showed that micronucleation provides an effective means of removing extrachromosomally amplified genes from tumor cells, and for reducing tumorigenicity through induction of differentiation or apoptosis. The research conducted in the past year was designed to determine the mechanisms of micronucleation and to identify new agents that could induce this process. We report that micronuclei can be generated during S-phase by nuclear budding. This represents a process that has not been reported previously. We show that micronucleation can be induced by a broad spectmm of antiproliferative agents that impede replication fork progression. Micronucleation occurred at low frequency in cells with a functional p53 pathway, but eliminating p53 function substantially increased micronucleation efficiency. Since p53 deficiency and gene amplification occur in vivo only in tumors, the results indicate that treatments that induce micronuclei should be highly selective for neoplasms. We also show that micronuclei are generated during tumor growth in vivo, and preliminary results indicate that purification of such structures directly from disaggregated tumor tissue may provide a diagnostic method for DMs and for specifying the chromosomal location(s) from which they arose.

Descriptors :   *NEOPLASMS, *DIAGNOSIS(MEDICINE), *GENES, *CELLS(BIOLOGY), *GROWTH(PHYSIOLOGY), *BREAST CANCER, POSITION(LOCATION), TISSUES(BIOLOGY), MOLECULES, TARGETS, CHROMOSOMES, PURIFICATION, AMPLIFICATION, IN VIVO ANALYSIS, LOW FREQUENCY.

Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE