Inhibition of angiogenesis by the BTB domain of promyelocytic leukemia zinc finger protein.
Promyelocytic leukemia zinc finger is a negative regulator of cell cycle progression. In this study, we showed that PLZF inhibits endothelial cell angiogenesis using a human umbilical vein endothelial cell system. We also focused on characterizing the specific function of the BTB domain of PLZF as a novel apoptotic and anti-angiogenic protein via deletion mapping analysis. The BTB domain directly inhibited tube formation, as well as the biological functions of angiostatic activity in vivo, and reduced the expression of p-Akt and p-eNOS, which play a significant role in angiogenesis when stimulated by VEGF. These results strongly suggest that the BTB domain could potentially modulate the apoptotic and anti-angiogenic effects of PLZF.
Rho
Seung Bae
SB
Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea. sbrho@ncc.re.kr
Choi
Kyusam
K
Park
Kyoungsook
K
Lee
Je-Ho
JH
D000818:Animals; D002453:Cell Cycle; D002465:Cell Movement; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000502:physiology; D003001:Cloning, Molecular; D056751:Cyclin A2 / Q000235:genetics; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005312:Fetal Blood; D017353:Gene Deletion; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016185:Receptors, Interleukin-3 / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic; D014470:Umbilical Cord; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
D056751:Cyclin A2; D017931:DNA Primers; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D034741:RNA, Small Interfering; D016185:Receptors, Interleukin-3; C092037:ZBTB16 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D013936:Thymidine