Induction of cellular senescence in a telomerase negative human immortal fibroblast cell line, LCS-AF.1-3, by human chromosome 6

Kumata,M.; Shimizu,M.; Oshimura,M.; Uchida,M.; Tsutsui,T.

doi:10.3892/ijo.21.4.851

October 2002 Volume 21 Issue 4

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October 2002 Volume 21 Issue 4

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Article

Induction of cellular senescence in a telomerase negative human immortal fibroblast cell line, LCS-AF.1-3, by human chromosome 6

Authors:
- M. Kumata
- M. Shimizu
- M. Oshimura
- M. Uchida
- T. Tsutsui
View Affiliations / Copyright

Affiliations: Oral and Maxillofacial Surgery, The Nippon Dental University Hospital at Tokyo, Tokyo 102-8158, Japan
Pages: 851-856
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Published online on: October 1, 2002

https://doi.org/10.3892/ijo.21.4.851
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Abstract

In immortal cells (LCS-AF.1-3) which originated from cultured skin fibroblasts from a patient with Li-Fraumeni syndrome, a specific deletion has been identified on chromosome 6. To examine the relationship between this deletion and the loss of function in aging genes, we performed microcell mediated chromosome transfer (MMCT) of normal human chromosome 6 into LCS-AF.1-3 cells and analyzed their characteristics. Transferred human chromosome 6 induced morphological changes in the cells and cellular senescence with growth suppression. In a revertant clone that had escaped from induced senescence, a specific deletion was found at D6S309 in the transferred chromosome 6. High molecular weight telomeric sequences were lost in a clone that had been induced to senescence by introduction of human chromosome 6. On the other hand, human chromosome 7 induces senescence in immortal cells by suppressing the alternative lengthening of telomere (ALT) mechanism. We also performed MMCT of chromosome 7 and discuss the effect of chromosome transfer by comparing the two chromosomes. LCS-AF.1-3 cells containing a transferred chromosome 7 showed no changes in immortality. These results suggest that genes which are new candidates for aging and which suppress the ALT mechanism are located in the region D6S309 in human chromosome 6.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Induction of cellular senescence in a telomerase negative human immortal fibroblast cell line, LCS-AF.1-3, by human chromosome 6

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