Transforming growth factor β triggers two independent-senescence programs in cancer cells

Transforming growth factor-β (TGF-β)TG has been shown to play a multifunctional role in tumorigenesis. Here we demonstrate that TGF-β induces a morphological change and expression of senescence-associated β-galactosidase activity in the human lung adenocarcinoma cell line A549 cells within a week after the addition. These TGF-β induced phenotypic changes are thought to characterize the rapid onset of senescence. When A549 cells were treated with TGF-β, cell growth was not completely arrested, but the activity of telomerase was down regulated via transcriptional repression of telomerase reverse transcriptase, which led to a shortening of the telomere during long-term culture and finally resulted in replicative senescence. These results indicate that TGF-β is able to induce a rapid senescence in A549 cells without significantly inhibiting cell growth and can further direct A549 cells to a replicative senescence state via the suppression of telomerase which culminates in telomere shortening. All these experimental results suggest that TGF-β transmits several separate and independent signals to shift A549 cells back to a normal senescent cell.