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

Transforming growth factor-beta (TGF-beta)TG has been shown to play a multifunctional role in tumorigenesis. Here we demonstrate that TGF-beta induces a morphological change and expression of senescence-associated beta-galactosidase activity in the human lung adenocarcinoma cell line A549 cells within a week after the addition. These TGF-beta induced phenotypic changes are thought to characterize the rapid onset of senescence. When A549 cells were treated with TGF-beta, 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-beta 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-beta transmits several separate and independent signals to shift A549 cells back to a normal senescent cell. Copyright 1999 Academic Press.