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Research article

Mechanism of apoptotic cell death of human gastric carcinoma cells mediated by transforming growth factor β

Shigeki OHTA, Kazuyoshi YANAGIHARA, Kiyoshi NAGATA
Biochemical Journal Jun 15, 1997, 324 (3) 777-782; DOI: 10.1042/bj3240777
Shigeki OHTA
Shionogi Research Laboratories, Shionogi and Co., Ltd., 5-12-4 Sagisu, Fukushima-ku, Osaka, Osaka 553, Japan
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Kazuyoshi YANAGIHARA
Department of Pathology, Research Institute for Nuclear Medicine and Biology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734, Japan
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Kiyoshi NAGATA
Shionogi Research Laboratories, Shionogi and Co., Ltd., 5-12-4 Sagisu, Fukushima-ku, Osaka, Osaka 553, Japan
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Abstract

Human gastric carcinoma cell line HSC-39 has been shown to undergo apoptotic cell death in response to treatment with transforming growth factor β1 (TGF-β1). To understand better the cell death mechanism in this TGF-β1-mediated apoptosis, we investigated the effect of the expression of TGF-β-stimulated clone 22 (TSC-22) on cell death events. TGF-β1 induced TSC-22 gene expression in HSC-39 cells only when the cells had previously been adapted to the serum-free culture conditions required to undergo TGF-β1-mediated apoptosis. HSC-39 cells transfected with a TSC-22 expression vector showed a significant decrease in cell viability compared with those transfected with a control vector. The cellular events characteristic of apoptosis, chromatin condensation and DNA fragmentation were observed only in cells transfected with a TSC-22 expression vector. On immunostaining of the transfected cells, almost every cell that expressed TSC-22 tagged with influenza virus haemagglutinin exhibited the morphology of an apoptotic cell. Partial protection from the cell death effect of TGF-β1 on HSC-39 cells was observed when cells were treated with acetyl-l-aspartyl-l-glutamyl-l-valyl-l-aspart-1-al (Ac-DEVD-CHO, an inhibitor specific for CPP32-type protease). Protection against cell death by the transfection of a TSC-22 expression vector was also offered by Ac-DEVD-CHO addition. These results suggest that TSC-22 elicits the apoptotic cell death of human gastric carcinoma cells through the activation of CPP32-like protease and mediates the TGF-β1 signalling pathway to apoptosis.

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June 1997

Volume: 324 Issue: 3

Biochemical Journal: 324 (3)
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Mechanism of apoptotic cell death of human gastric carcinoma cells mediated by transforming growth factor β
Shigeki OHTA, Kazuyoshi YANAGIHARA, Kiyoshi NAGATA
Biochemical Journal Jun 1997, 324 (3) 777-782; DOI: 10.1042/bj3240777
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Mechanism of apoptotic cell death of human gastric carcinoma cells mediated by transforming growth factor β
Shigeki OHTA, Kazuyoshi YANAGIHARA, Kiyoshi NAGATA
Biochemical Journal Jun 1997, 324 (3) 777-782; DOI: 10.1042/bj3240777

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