Expression of promyelocytic leukemia protein increases during the differentiation of human neuroblastoma cells.
The promyelocytic leukemia (PML) protein, whose fusion with retinoic acid receptor alpha is responsible for the tumorigenesis of acute promyelocytic leukemia, acts as a tumor suppressor in various types of human cancers. We analyzed the expression patterns of PML, in both primary neuroblastic tumors ( n=20) and two human neuroblastoma (NB) cell lines, SMS-KCNR (KCNR) and SH-SY5Y (SY5Y). The expression of PML, revealed as speckled or microgranular staining in the nuclei, was positively correlated with the differentiation status of NB cells in vivo, and was upregulated during the differentiation of KCNR and SY5Y cells following retinoic acid treatment. Screening of PML expression in human brain and sympathetic ganglia showed restricted expression of PML in mature neurons and glial cells, a result that was consistent with that in differentiated NB tumors. All these findings strongly suggest that increased PML expression is associated with growth inhibition and differentiation of human NB cells, and that it is of critical significance in the biology of NBs and in human nervous system development.
Yu
Eunsil
E
Department of Diagnostic Pathology, University of Ulsan College of Medicine, Asan Medical Center, 138-736, Seoul, Korea.
Choi
Eun Kyung
EK
Kim
Chong Jai
CJ
D000293:Adolescent; D002454:Cell Differentiation; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis*; D009447:Neuroblastoma / Q000473:pathology*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000032:analysis*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D014212:Tretinoin