Thwarting PTEN Expression by siRNA Augments HL-60 Cell Differentiation to Neutrophil-Like Cells by DMSO and ATRA.
Abnormal cell differentiation, in particular suppression of terminal cell differentiation, exists in all tumors. Therapeutic interventions to restore terminal differentiation ("differentiation therapy") are a very attractive way to treat cancer, especially leukemia. A variety of chemicals stimulates differentiation of leukemic cells, such as dimethyl sulfoxide (DMSO) and all-trans retinoic acid (ATRA). Tumor suppressor genes have a vital role in the gateway to terminal cell differentiation. In this study, we inhibited PTEN tumor suppressor gene expression by siRNA to investigate the effect of potentiating cell survival and inhibiting apoptosis on HL-60 cell differentiation by DMSO and ATRA. Our results show that PTEN siRNA increases HL-60 cell differentiation in the presence of DMSO and ATRA. At the same time, the presence of siRNA hampers accumulation of apoptotic cells during incubation. Our study suggests that manipulation of PTEN could hold promise for enhancing efficacy of differentiation therapy of acute myelogenous leukemia.
1 Department of Medical Genetics, Iran University of Medical Sciences , Tehran, Iran .|2 Department of Human Genetics, Tehran University of Medical Sciences , Tehran, Iran .|3 Department of Infectious Diseases, Pediatrics Infectious Diseases Research Center, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran .
Shahram
S
Teimourian
2 Department of Human Genetics, Tehran University of Medical Sciences , Tehran, Iran .|3 Department of Infectious Diseases, Pediatrics Infectious Diseases Research Center, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran .|4 Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences , Kashan, Iran .
Ehsan
E
Moghanloo
D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D009504:Neutrophils / Q000166:cytology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors*; D034741:RNA, Small Interfering; D014212:Tretinoin / Q000494:pharmacology*
D034741:RNA, Small Interfering; D014212:Tretinoin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D004121:Dimethyl Sulfoxide
HL-60; PTEN; differentiation therapy; downregulation; neutrophil