Lee Young-Rae, Yu Hong-Nu, Noh Eun-Mi, Youn Hyun Jo, Song Eun-Kyung, Han Myung-Kwan, Park Chang-Sik, Kim Byung-Soo, Park Young-Seok, Park Byung-Kwon, Lee Sung-Ho, Kim Jong-Suk
Department of Biochemistry, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Exp Mol Med. 2007 Feb 28;39(1):121-7. doi: 10.1038/emm.2007.14.
TNF-alpha plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between the two molecules are suggested. TNF-alpha has been known to downregulate PTEN via NF-kappaB pathway in the human colon cell line, HT-29. However, here we show the opposite finding that TNF-alpha upregulates PTEN via activation of NF-kappaB in human leukemic cells. TNF-alpha increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of NF-kappaB with p65 antisense phosphorothioate oligonucleotide or pyrrolidine dithiocarbamate. We found that TNF-alpha activated the NF-kappaB pathways, evidenced by the translocation of p65 to the nucleus in TNF-alpha-treated cells. We conclude that TNF-alpha induces upregulation of PTEN expression through NF-kappaB activation in human leukemic cells.
肿瘤坏死因子-α（TNF-α）发挥多种生物学功能，如细胞凋亡、炎症和免疫。磷酸酶和张力蛋白同源物（PTEN）也具有多种细胞功能，包括细胞生长、增殖、迁移和分化。因此，提示了这两种分子之间可能存在的关系。已知在人结肠癌细胞系HT-29中，TNF-α通过核因子-κB（NF-κB）途径下调PTEN。然而，在此我们展示了相反的发现，即TNF-α在人白血病细胞中通过激活NF-κB上调PTEN。TNF-α以时间和剂量依赖性方式增加HL-60细胞中PTEN的表达，但用p65反义硫代磷酸酯寡核苷酸或吡咯烷二硫代氨基甲酸盐破坏NF-κB可消除该反应。我们发现TNF-α激活了NF-κB途径，这通过TNF-α处理的细胞中p65易位至细胞核得以证明。我们得出结论，TNF-α通过激活NF-κB诱导人白血病细胞中PTEN表达上调。
