TGF-β-1 up-regulates cyclin D1 expression in colo-357 cells, whereas suppression of cyclin d1 levels is associated with down-regulation of the type I TGF-β receptor
✍ Scribed by Marko Kornmann; Pam Tangvoranuntakul; Murray Korc
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 174 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Transforming growth factor-1 (TGF-1) inhibits cell growth in susceptible cells by interacting with a family of protein kinases that control cell cycle progression. In the present study, we investigated the effects of TGF-1 on cyclin D1 expression and activity in COLO-357 human pancreatic cancer cells. TGF-1 increased cyclin D1 mRNA and protein levels. Nuclear runoff transcription and protein synthesis inhibition by cycloheximide revealed that this increase was, in part, due to increased cyclin D1 mRNA synthesis. Despite its stimulatory effects on cyclin D1 levels, TGF-1 inhibited cyclin D1-associated kinase activity and the growth of COLO-357 cells. Furthermore, suppression of cyclin D1 expression with a cyclin D1 antisense cDNA resulted in loss of TGF-1mediated growth inhibition in association with reduced induction of cyclin D1, p21 Cip1 and plasminogen activator inhibitor-1 (PAI-1). Concomitantly, there was a marked decrease in the levels of the type I TGF- receptor (TRI). Our findings suggest that in some cell types cyclin D1 expression may be important for TGF-1-mediated signaling and that cyclin D1 may be involved in the transcriptional regulation of TRI. Int.