Caspase-3 inhibits the growth of breast cancer cells independent of protease activity

被引:9
作者
Faraglia, B
Bonsignore, A
Scaldaferri, F
Boninsegna, A
Cittadini, A
Mancuso, C
Sgambato, A
机构
[1] Catholic Univ, Sch Med, Ist Farmacol, I-00168 Rome, Italy
[2] Ctr Ric Oncol Giovanni XXIII, Ist Patol Gen, Rome, Italy
关键词
D O I
10.1002/jcp.20149
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In this study, the MCF-7 breast cancer cells that lack caspase-3 were transfected with a wild type (WT) or mutant caspase-3 cDNA. Expression of the WT, but not of the mutant, caspase-3 was associated with increased caspase activity and susceptibility to staurosporine (STS)-induced apoptosis. Both derivatives displayed inhibition of cell growth compared with vector control cells. Growth inhibition was associated with increased expression of the cyclin dependent kinase (CDK) inhibitor P27(Kip1) in the WT, but not in the mutant caspase-3 expressing cells. Cyclin D1 expression level was not affected by caspase-3 expression. Phosphorylation of the Akt protein was decreased in both WT and mutant caspase transfected cells, although Akt expression level remained unchanged. These results suggest that caspase-3 might have biological functions independent of its protease activity and that its loss might contribute to tumor development by increasing the growth potential of cancer cells. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:478 / 482
页数:5
相关论文
共 28 条
[1]  
Chan SL, 1999, J NEUROSCI RES, V58, P167, DOI 10.1002/(SICI)1097-4547(19991001)58:1<167::AID-JNR16>3.3.CO
[2]  
2-B
[3]  
COHEN JJ, 1992, ANNU REV IMMUNOL, V10, P267, DOI 10.1146/annurev.iy.10.040192.001411
[4]   APOPTOTIC CELL-DEATH INDUCED BY A MOUSE-HUMAN ANTI-APO-1 CHIMERIC ANTIBODY LEADS TO TUMOR-REGRESSION [J].
CONEY, LR ;
DANIEL, PT ;
SANBORN, D ;
DHEIN, J ;
DEBATIN, KM ;
KRAMMER, PH ;
ZURAWSKI, VR .
INTERNATIONAL JOURNAL OF CANCER, 1994, 58 (04) :562-567
[5]   Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance [J].
Devarajan, E ;
Sahin, AA ;
Chen, JS ;
Krishnamurthy, RR ;
Aggarwal, N ;
Brun, AM ;
Sapino, A ;
Zhang, F ;
Sharma, D ;
Yang, XH ;
Tora, AD ;
Mehta, K .
ONCOGENE, 2002, 21 (57) :8843-8851
[6]   MECHANISMS AND FUNCTIONS OF CELL-DEATH [J].
ELLIS, RE ;
YUAN, JY ;
HORVITZ, HR .
ANNUAL REVIEW OF CELL BIOLOGY, 1991, 7 :663-698
[7]   Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance [J].
Friedrich, K ;
Wieder, T ;
Von Haefen, C ;
Radetzki, S ;
Jänicke, R ;
Schulze-Osthoff, K ;
Dörken, B ;
Daniel, PT .
ONCOGENE, 2001, 20 (22) :2749-2760
[8]   Apoptosis-inducing effect of recombinant Caspase-3 expressed by constructed eukaryotic vector on gastric cancer cell line SGC7901 [J].
Fu, YG ;
Qu, YJ ;
Wu, KC ;
Zhai, HH ;
Liu, ZG ;
Fan, DM .
WORLD JOURNAL OF GASTROENTEROLOGY, 2003, 9 (09) :1935-1939
[9]  
GERARD GI, 2001, NATURE, V411, P342
[10]   Apoptosis and metastasis: Increased apoptosis resistance of metastatic cancer cells is associated with the profound deficiency of apoptosis execution mechanisms [J].
Glinsky, GV ;
Glinsky, VV ;
Ivanova, AB ;
Hueser, CJ .
CANCER LETTERS, 1997, 115 (02) :185-193