TNF-alpha upregulates PTEN via NF-kappaB signaling pathways in human leukemic cells.
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.
Lee
Young-Rae
YR
Department of Biochemistry, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Yu
Hong-Nu
HN
Noh
Eun-Mi
EM
Youn
Hyun Jo
HJ
Song
Eun-Kyung
EK
Han
Myung-Kwan
MK
Park
Chang-Sik
CS
Kim
Byung-Soo
BS
Park
Young-Seok
YS
Park
Byung-Kwon
BK
Lee
Sung-Ho
SH
Kim
Jong-Suk
JS
D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human