Human chromosome 3 mediates growth arrest and suppression of apoptosis in microcell hybrids.
Chemotherapeutic treatment of tumor cells leads either to tumor cell death (usually by apoptosis) or to the formation of drug-resistant subpopulations. Known mechanisms of cancer cell drug resistance include gene amplification and increased expression of drug transporters. On the other hand, normal cells survive many forms of chemotherapy with minimal damage probably because of their capacity for growth arrest and stringent control of apoptosis. Microcell hybrids between B78 (murine melanoma) and HSF5 (normal human fibroblasts) were analyzed to identify a new human chromosomal region involved in the promotion of drug-induced growth arrest and suppression of apoptosis. In these hybrids, the presence of human chromosome 3 was strongly associated with suppression of apoptosis via G1 and G2 growth arrest during exposure to the antimetabolite N-phosphonoacetyl-L-aspartate (PALA), suggesting that a gene(s) on chromosome 3 serves an antiproliferative role in a drug-responsive growth arrest pathway.
Speevak
M D
MD
Department of Biochemistry, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Chevrette
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D002588:Cesium Radioisotopes; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D005347:Fibroblasts; D005434:Flow Cytometry; D016193:G1 Phase; D016195:G2 Phase; D005720:Gamma Rays; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D008546:Melanoma, Experimental; D051379:Mice; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D002588:Cesium Radioisotopes; D005819:Genetic Markers; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid