Document Detail

The p16 (CDKN2A) gene is involved in the growth of neuroblastoma cells and its expression is associated with prognosis of neuroblastoma patients.
MedLine Citation:
PMID:  9872329     Owner:  NLM     Status:  MEDLINE    
We previously reported that loss of heterozygosity (LOH) on chromosome 9p21 correlates with poor prognosis of neuroblastoma and the p16 gene is not expressed in approximately two thirds of neuroblastoma cell lines. Here we demonstrated that p16 expression was induced by 5-aza-2-deoxycytidine treatment in cell lines with 5' CpG island methylation but not in cell lines without methylation. Furthermore, the cell cycle of neuroblastoma cell lines significantly delayed with accumulation of cells in G1 phase by transfection of a wild-type p16 expression vector. These results indicate that p16 is inactivated in part by DNA methylation and its expression is involved in the growth of neuroblastoma cells in vitro. To assess the biological and clinical significance of p16 expression in primary tumors, we undertook immunohistochemical analysis in 74 paraffin sections of neuroblastomas. p16 protein was undetectable in 45 of 74 cases (61%) and lack of p16 expression significantly correlated with poor prognosis of patients and advanced stage of the disease. There was no correlation between loss of p16 expression and N-myc amplification in these tumors. These results indicate that inactivation of the p16 gene is involved in the progression of neuroblastoma independently of N-myc amplification.
J Takita; Y Hayashi; T Nakajima; J Adachi; T Tanaka; N Yamaguchi; Y Ogawa; R Hanada; K Yamamoto; J Yokota
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  17     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-01-26     Completed Date:  1999-01-26     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  3137-43     Citation Subset:  IM    
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
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MeSH Terms
Azacitidine / analogs & derivatives,  pharmacology
Cell Division
Cyclin-Dependent Kinase Inhibitor p16 / genetics*,  metabolism
DNA Modification Methylases / antagonists & inhibitors
Enzyme Inhibitors / pharmacology
Gene Expression Regulation, Neoplastic* / drug effects
Neuroblastoma / pathology*
Tumor Cells, Cultured
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p16; 0/Enzyme Inhibitors; 320-67-2/Azacitidine; 776B62CQ27/decitabine; EC 2.1.1.-/DNA Modification Methylases

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