Expression and role of DJ-1 in leukemia.
DJ-1 is a multifunctional protein that has been implicated in pathogenesis of some solid tumors. In this study, we found that DJ-1 was overexpressed in acute leukemia (AL) patient samples and leukemia cell lines, which gave the first clue that DJ-1 overexpression might be involved in leukemogenesis and/or disease progression of AL. Inactivation of DJ-1 by RNA-mediated interference (RNAi) in leukemia cell lines K562 and HL60 resulted in inhibition of the proliferation potential and enhancement of the sensitivity of leukemia cells to chemotherapeutic drug etoposide. Further investigation of DJ-1 activity revealed that phosphatase and tensin homolog (PTEN), as well as some proliferation and apoptosis-related genes, was regulated by DJ-1. Thus, DJ-1 might be involved in leukemogesis through regulating cell growth, proliferation, and apoptosis. It could be a potential therapeutic target for leukemia.
Liu
Hang
H
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Wang
Min
M
Li
Min
M
Wang
Donghai
D
Rao
Qing
Q
Wang
Yang
Y
Xu
Zhifang
Z
Wang
Jianxiang
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D014176:Protein Biosynthesis / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D005047:Etoposide; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human