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Proapoptotic activity of NAG-1 is cell type specific and not related to COX-2 expression

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Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) activated gene (NAG-1) is a newly identified member of the transforming growth factor-β (TGF-β) superfamily. Members of the TGF-β family are multifunctional growth factors, and the nature of their effects depends on the cellular context and cell type. NAG-1 has antitumorigenic and proapoptotic activities in colon and gastric cancer cells lacking endogenous cyclooxgenase-2 (COX-2) expression. In contrast, COX-2 overexpression is related to antiapoptotic activity. The purpose of this study is to evaluate the proapoptotic activity of NAG-1 according to COX-2 expression and cell type. NAG-1 cDNA was transfected in SNU668 cells with endogenous COX-2 expression, SNU601 cells with forced COX-2 expression and Hep3B hepatocellular carcinoma cells. SNU668 cells with ectopic expression of NAG-1 showed markedly elevated subG1 population, induced death receptor-4 (DR-4) and DR-5, and revealed smaller active fragments of caspase-3. Forced COX-2 expression in SNU601 cells did not inhibit apoptosis caused by NAG-1 expression. Sulindac sulfide caused apoptosis, and induced expression of DR-5 and NAG-1 in Hep3B cells. However, Hep3B cells ectopically expressing NAG-1 did not cause apoptosis, and smaller active fragments of caspase-3 and an 85 kDa band of poly ADP-ribose polymerase (PARP) did not appear in the transfected cells, either. This study suggests that proapoptotic activity of NAG-1 is cell type specific and not related to COX-2 expression.

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Authors and Affiliations

  1. Department of Pathology, Dongguk University College of Medicine, Suek-jang Dong 707, Kyongju, Kyongbuk, 780-714, Korea

    Tae Jung Jang

  2. Department of Gastroenterology, Dongguk University College of Medicine, Kyongbuk, Korea

    Nam II Kim

  3. Department of Pathology, Pusan National University College of Medicine, Pusan, Korea

    Chang Hun Lee

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  1. Tae Jung Jang
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  2. Nam II Kim
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  3. Chang Hun Lee
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Correspondence to Tae Jung Jang.

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Jang, T.J., Kim, N.I. & Lee, C.H. Proapoptotic activity of NAG-1 is cell type specific and not related to COX-2 expression. Apoptosis 11, 1131–1138 (2006). https://doi.org/10.1007/s10495-006-8160-x

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