Identification of additional complementation groups that regulate genomic instability.
By somatic cell hybridization, amplification has been found to be a recessive genetic trait in three tumor cell lines examined. Studies with transgenic mice have shown that amplification frequency can be altered by a lack of wild-type TP53 (p53) activity. Other factors may regulate this phenotype in tumor cell lines possessing both wild-type p53 activity and amplification ability. Complementation analysis of somatic cell hybrids was performed to delineate groups of tumor cell lines that share a common defect that modulates the ability to amplify. The amplification frequencies of three normal fibroblast x tumor hybrids were suppressed 10-100-fold from parental tumor values, extending the observation that amplification is a recessive genetic characteristic in these cell lines. Analysis of tumor x tumor hybrids revealed at least two complementation groups. Defects in these groups differed from TP53 and implicate multiple variables in the regulation of gene amplification.
Hall
I J
IJ
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, USA.
Gioeli
D
D
Weissman
B E
BE
Tlsty
T D
TD
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001221:Aspartate Carbamoyltransferase / Q000235:genetics*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics*; D002453:Cell Cycle; D004080:Dihydroorotase / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005347:Fibroblasts; D005784:Gene Amplification / Q000235:genetics*; D005808:Genes, Recessive; D016158:Genes, p53 / Q000235:genetics*; D005816:Genetic Complementation Test; D006801:Humans; D006822:Hybrid Cells; D009097:Multienzyme Complexes / Q000235:genetics*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000964:Antimetabolites, Antineoplastic; C033626:CAD trifunctional enzyme; D009097:Multienzyme Complexes; D001224:Aspartic Acid; C013195:sparfosic acid; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D010746:Phosphonoacetic Acid