Abstract:
:Defining apoptosis-regulatory cascades of the epithelium is important for understanding carcinogenesis, since cancer cells are considered to arise as a result of the collapse of the cascades. We previously reported that a novel gene GASDERMIN (GSDM) is expressed in the stomach but suppressed in gastric cancer cell lines. Furthermore, in this study, we demonstrated that GSDM is expressed in the mucus-secreting pit cells of the gastric epithelium and frequently silenced in primary gastric cancers. We found that GSDM has a highly apoptotic activity and its expression is regulated by a transcription factor LIM domain only 1 (LMO1) through a sequence to which Runt-related transcription factor 3 (RUNX3) binds, in a GSDM promoter region. We observed coexpression of GSDM with LMO1, RUNX3 and type II transforming growth factor-beta receptor (TGF-betaRII) in the pit cells, and found that TGF-beta upregulates the LMO1- and GSDM-expression in the gastric epithelial cell line and induces apoptosis, which was confirmed by the finding that the apoptosis induction is inhibited by suppression of each LMO1-, RUNX3- and GSDM expression, respectively. The present data suggest that TGF-beta, LMO1, possibly RUNX3, and GSDM form a regulatory pathway for directing the pit cells to apoptosis.
journal_name
Oncogenejournal_title
Oncogeneauthors
Saeki N,Kim DH,Usui T,Aoyagi K,Tatsuta T,Aoki K,Yanagihara K,Tamura M,Mizushima H,Sakamoto H,Ogawa K,Ohki M,Shiroishi T,Yoshida T,Sasaki Hdoi
10.1038/sj.onc.1210475subject
Has Abstractpub_date
2007-10-04 00:00:00pages
6488-98issue
45eissn
0950-9232issn
1476-5594pii
1210475journal_volume
26pub_type
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