Abstract
Transforming growth factor-β (TGF-β) has been demonstrated to regulate extracellular matrix formation, cell differentiation, and cell cycle in most cell types. Here we demonstrate that TGF-β induces a premature senescence in A549 cells (human lung adenocarcinoma cell line) independently of the telomere shortening, which was evidenced by the expression of senescence marker β-galactosidase and morphological changes. However, A549 cells did not completely inhibit for its growth by the treatment of TGF-β, which was thought to be one of key features of premature senescence. These results suggest that the induction of premature senescence and growth inhibition are independently regulated in the TGF-β treated A549 cells. On the other hand, telomerase activity was downregulated via transcriptional repression of hTERT (human reverse transcriptase) in the TGF-β treated A549 cells. Furthermore, when A549 cells was cultured with TGF-β for a long term, telomere length gradually shortened from 8 kb to 2 kb. These resultsindicate A549 cells treated with TGF-β entered into the replicative senescence state. This study provides a new correlation between TGF-β signals and a cellular senescence programs.
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© 1999 Kluwer Academic Publishers
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Miura, T., Katakura, Y., Nakata, E., Uehara, N., Shirahata, S. (1999). TGF-β Induces Premature and Replicative Senescence in Cancer Cells. In: Bernard, A., Griffiths, B., Noé, W., Wurm, F. (eds) Animal Cell Technology: Products from Cells, Cells as Products. Springer, Dordrecht. https://doi.org/10.1007/0-306-46875-1_33
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DOI: https://doi.org/10.1007/0-306-46875-1_33
Publisher Name: Springer, Dordrecht
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