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The microsatellite mutator phenotype of colon cancer cells is often recessive
Author(s): Casares S, Ionov Y, Ge HY, Stanbridge E, Perucho M
Source: ONCOGENE    Volume: 11    Issue: 11    Pages: 2303-2310    Published: DEC 7 1995  
Times Cited: 38     References: 51     
Abstract: A new mutator mechanism for tumorigenesis, characterized by somatic genomic instability (SGI) at simple repeated sequences (SRS) or microsatellites, underlies hereditary nonpolyposis colorectal cancer (HNPCC) and some sporadic tumors of the colon and other types, To determine whether the microsatellite mutator phenotype (MMP) is dominant or recessive, we generated somatic cell hybrids between a tumor cell line without SGI at SRS (D98OR) and colon carcinoma cell lines with relative low (HCT-15) and high (LS174-T) SGI at SRS, The normal fidelity of replication of these unstable sequences was observed in each of these cell hybrids, Fusion of HCT-1S/DLD-1 low instability cells, with LS174-T, HCT116 and LoVo cell Lines, all exhibiting relative high instability, also restored the replication fidelity of SRS in all of the hybrids, Hybrids between the high instability cell lines did not grow possibly because of senescence or apoptosis, These results indicate that, in the cell lines analysed, the characterized mutator phenotype of the mismatch repair system resulting in high SGI at SRS, and the uncharacterized mutator phenotype underlying low SGI at SRS, are both recessive, The results also suggest that different tumor cells of the MMP harbor distinct altered growth-related genes.
Document Type: Article
Language: English
Addresses:
1. CALIF INST BIOL RES, LA JOLLA, CA 92037 USA
2. UNIV CALIF IRVINE, DEPT MICROBIOL & MOLEC GENET, IRVINE, CA 92717 USA
Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS
Subject Category: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
IDS Number: TK702
ISSN: 0950-9232
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