Transforming growth factor-beta 1-induced Smad signaling, cell-cycle arrest and apoptosis in hepatoma cells

Citation
Cl. Buenemann et al., Transforming growth factor-beta 1-induced Smad signaling, cell-cycle arrest and apoptosis in hepatoma cells, CARCINOGENE, 22(3), 2001, pp. 447-452
Citations number
42
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
01433334 → ACNP
Volume
22
Issue
3
Year of publication
2001
Pages
447 - 452
Database
ISI
SICI code
0143-3334(200103)22:3<447:TGF1SS>2.0.ZU;2-S
Abstract
Transforming growth factor-beta (TGF beta) is involved in the regulation of liver cell proliferation and apoptosis, and escape of hepatoma cells from the growth restraining signals of TGF beta has been suggested to contribute to tumor development. TGF beta modulates gene transcription by receptor-me diated activation of Smad proteins which act as transcription factors. TGF beta -mediated primary signaling responses as well as effects on the cell c ycle and apoptosis were investigated in the human hepatoblastoma line HepG2 , the rat hepatoma line FTO-2B and the mouse hepatoma line 55.1c, Activatio n of a Smad (Sma and Mad homolog) response-element-driven luciferase report er by TGF beta was very similar in ail three cell lines, indicating functio nality of the primary TGF beta signaling pathway. Moreover, TGF beta -induc ible early gene was transiently activated by TGF beta in all cell lines as shown by RT-PCR, HepG2 cells, however, were completely resistant to TGF bet a -induced growth arrest and apoptosis and 55.1c cells were only slightly s usceptible to TGF beta -induced apoptosis, By contrast, treatment of FTO-2B cells with TGF beta led to a partial G(0)/G(1) arrest and a strong inducti on of apoptosis, TGF beta -induced apoptosis of FTO-2B cells was inhibited by dexamethasone, insulin, phenobarbital and dieldrin, Of these agents, onl y insulin led to a significant reduction of TGF beta -stimulated Smad-repor ter activity, suggesting that the other compounds interfere with TGF beta - induced apoptosis downstream of Smad-mediated primary transcriptional respo nses at a level that may be constitutively altered in apoptosis-resistant h epatoma cell lines.