TGF-β induces premature and replicative senescence in cancer cells

Transforming growth factor-beta (TGF-beta) has been demonstrated to regulate extracellular matrix formation, cell differentiation, and cell cycle in most cell types. Here we demonstrate that TGF-beta 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 beta-galactosidase and morphological changes. However, A549 cells did not completely inhibit for its growth by the treatment of TGF-beta, 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-beta treated A549 cells. On the other hand, telomerase activity was downregulated via transcriptional repression of hTERT (human reverse transcriptase) in the TGF-beta treated A549 cells. Furthermore, when A549 cells was cultured with TGF-beta for a long term, telomere length gradually shortened from 8 kb to 2 kb. These results indicate A549 cells treated with TGF-beta entered into the replicative senescence state. This study provides a new correlation between TGF-beta signals and a cellular senescence programs.