Differential response of p53 target genes to p73 overexpression in SH-SY5Y neuroblastoma cell line

被引:32
作者
Goldschneider, D
Blanc, E
Raguénez, G
Barrois, M
Legrand, A
Le Roux, G
Haddada, H
Bénard, J
Douc-Rasy, S
机构
[1] Inst Gustave Roussy, Genet Lab, CNRS, UMR 8126, F-94805 Villejuif, France
[2] Inst Gustave Roussy, Lab Genet, U362, INSERM, F-94805 Villejuif, France
关键词
neuroblastoma; p73; p53; apoptosis; differentiation;
D O I
10.1242/jcs.00834
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
p73, the first p53 gene homologue, encodes an array of p73 proteins including p73alpha full-length (TAp73alpha) and amino-truncated isoforms (DeltaNp73alpha), two proteins with opposite biological functions. TAp73alpha, can induce tumor suppressive properties, while DeltaNp73alpha antagonizes p53 as well as TAp73 in a dominant-negative manner. In human malignant neuroblasts, p53 protein is wild-type but known to be excluded from the nucleus, therefore disabling its function as a tumor suppressor. The present study investigates whether there is a functional link between p73 isoforms and p53 in neuroblastoma. Experiments were performed on two neuroblastoma cell lines differing in their p53 status, e.g. wild-type p53 SH-5Y5Y cells and mutated p53 IGR-N-91 cells. Data indicate that (i) both TA- and DeltaN-p73alpha enhance p53 protein level in SH-SY5Y cells, whereas level remains unchanged in IGR-N-91 cells; (ii) only in SH-SY5Y cells does forced TAp73alpha overexpression markedly induce nuclear accumulation of p53 protein; (iii) p21 protein expression is increased in both cell lines infected with TAp73, suggesting that, in IGR-N-91 cells, p21 is induced by p73 through a p53-independent pathway; (iv) in the SH-SY5Y cell line, Btg2 expression is strongly enhanced in cells overexpressing TA, and to a lesser extent in cells overexpressing DeltaN. Taken together our results suggest that TAp73 may restore p53 function in NB with wild-type nonfunctional p53, but not in NB with mutated p53.
引用
收藏
页码:293 / 301
页数:9
相关论文
共 44 条
[1]  
Appella E, 2000, PATHOL BIOL, V48, P227
[2]   The proliferation of normal human fibroblasts is dependent upon negative regulation of p53 function by mdm2 [J].
Blaydes, JP ;
Wynford-Thomas, D .
ONCOGENE, 1998, 16 (25) :3317-3322
[3]   Expression of ΔNp73 is a molecular marker for adverse outcome in neuroblastoma patients [J].
Casciano, I ;
Mazzocco, K ;
Boni, L ;
Pagnan, G ;
Banelli, B ;
Allemanni, G ;
Ponzoni, M ;
Tonini, GP ;
Romani, M .
CELL DEATH AND DIFFERENTIATION, 2002, 9 (03) :246-251
[4]   Induction of neuronal differentiation by p73 in a neuroblastoma cell line [J].
De Laurenzi, V ;
Raschellá, G ;
Barcaroli, D ;
Annicchiarico-Petruzzelli, M ;
Ranalli, M ;
Catani, MV ;
Tanno, B ;
Costanzo, A ;
Levrero, M ;
Melino, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (20) :15226-15231
[5]  
DEFROMENTEL CC, 1992, GENE CHROMOSOME CANC, V4, P1
[6]   Inactivation of the p53-homologue p73 by the mdm2-oncoprotein [J].
Dobbelstein, M ;
Wienzek, S ;
König, C ;
Roth, J .
ONCOGENE, 1999, 18 (12) :2101-2106
[7]   ΔN-p73α accumulates in human neuroblastic tumors [J].
Douc-Rasy, S ;
Barrois, M ;
Echeynne, M ;
Kaghad, M ;
Blanc, E ;
Raguenez, G ;
Goldschneider, D ;
Terrier-Lacombe, MJ ;
Hartmann, O ;
Moll, U ;
Caput, D ;
Bénard, J .
AMERICAN JOURNAL OF PATHOLOGY, 2002, 160 (02) :631-639
[8]   Accumulation of an inactive form of p53 protein in cells treated with TNFα [J].
Drané, P ;
Leblanc, V ;
Miro-Mur, F ;
Saffroy, R ;
Debuire, B ;
May, E .
CELL DEATH AND DIFFERENTIATION, 2002, 9 (05) :527-537
[9]   The human BTG2/TIS21/PC3 gene:: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene [J].
Duriez, C ;
Falette, N ;
Audoynaud, C ;
Moyret-Lalle, C ;
Bensaad, K ;
Courtois, S ;
Wang, Q ;
Soussi, T ;
Puisieux, A .
GENE, 2002, 282 (1-2) :207-214
[10]  
FERRANDIS E, 1994, CANCER RES, V54, P2256