Normal human chromosome 2 induces cellular senescence in the human cervical carcinoma cell line SiHa.
For identification of the chromosome carrying cellular senescence-inducing activity, normal human chromosome 2, 3, 6, 7, 9, 11, or 12 tagged with a selectable marker gene (neo) was introduced into the human cervical carcinoma cell line SiHa via microcell-mediated chromosome transfer. Seventy-six percent (158/207) of the G418-resistant clones obtained by the transfer of chromosome 2 showed a remarkable change in morphology (cells were flat), and 93% (147/158) of them ceased to divide (senesced) prior to 6-9 population doublings, whereas most of the clones generated by the transfer of other chromosomes exhibited a morphology similar to that of the parental cells and continued to grow. Chromosome analyses suggested that cells which escaped from senescence contained only a small fragment derived from the transferred chromosome 2, whereas the transferred chromosomes were apparently intact in most of the continuously growing microcell hybrids with introduction of other chromosomes. These results indicate that the normal human chromosome 2 carries a gene or genes that induce cellular senescence in SiHa cells.
Department of Molecular and Cell Genetics, School of Life Sciences, Faculty of Medicine, Tottori University, Japan.
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H
Uejima
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Mitsuya
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Kugoh
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Horikawa
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Oshimura
D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D002871:Chromosome Banding; D002889:Chromosomes, Human, Pair 2; D017931:DNA Primers; D005260:Female; D005819:Genetic Markers; D005821:Genetic Techniques; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D019868:Kanamycin Kinase; D007621:Karyotyping; D008875:Middle Aged; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D017931:DNA Primers; D005819:Genetic Markers; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase