TRAIL is a key target in S-phase slowing-dependent apoptosis induced by interferon-beta in cervical carcinoma cells.

Abstract:

:Interferon (IFN)-beta induces S-phase slowing and apoptosis in human papilloma virus (HPV)-positive cervical carcinoma cell line ME-180. Here, we show that apoptosis is a consequence of the S-phase lengthening imposed by IFN-beta, demonstrating the functional correlation between S-phase alteration and apoptosis induction. In ME-180 cells, where p53 function is inhibited by HPV E6 oncoprotein, IFN-beta effects on cell cycle and apoptosis occur independently of p53. The apoptosis due to IFN-beta is mediated by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a manner dependent on the S-phase deregulation. IFN-beta appears to increase TRAIL expression both directly at the mRNA level and indirectly by augmenting surface protein levels as a consequence of the induced S-phase cell accumulation. Moreover, the alteration of the S-phase due to IFN-beta promotes TRAIL-dependent apoptosis by potentiating cell sensitivity to TRAIL, possibly through induction of a proapoptotic NF-kappaB activity and TRAIL-R2 receptor expression. Interestingly, IFN-beta-induced TRAIL-dependent apoptotic events strongly differ in the requirement of caspase activity. These results show that IFN-beta may induce an apoptotic response by deregulating cell cycle. Understanding the linkage between these mechanisms appears to be of primary importance in the search for new IFN-based therapeutic strategies to circumvent cancer disease or improve clinical outcome.

journal_name

Oncogene

journal_title

Oncogene

authors

Vannucchi S,Chiantore MV,Fiorucci G,Percario ZA,Leone S,Affabris E,Romeo G

doi

10.1038/sj.onc.1208403

subject

Has Abstract

pub_date

2005-04-07 00:00:00

pages

2536-46

issue

15

eissn

0950-9232

issn

1476-5594

pii

1208403

journal_volume

24

pub_type

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