Anti-Her-2/neu antibody induces apoptosis in Her-2/neu overexpressing breast cancer cells independently from p53 status

被引:20
作者
Brodowicz, T
Kandioler, D
Tomek, S
Ludwig, C
Rudas, M
Kunstfeld, R
Koestler, W
Hejna, M
Budinsky, A
Krainer, M
Wiltschke, C
Zielinski, CC [1 ]
机构
[1] Univ Hosp Vienna, Clin Div Oncol, Vienna, Austria
[2] Univ Hosp Vienna, Chair Med Expt Oncol, Dept Med 1, Vienna, Austria
[3] Univ Hosp Vienna, Dept Surg, Clin Div Gen Surg, Vienna, Austria
[4] Univ Hosp Vienna, Dept Pathol, Clin Div Clin Pathol, Vienna, Austria
[5] Ludwig Boltzman Inst Clin Expt Oncol, Vienna, Austria
关键词
apoptosis; bcl-2; breast cancer; HER-2/neu; p53;
D O I
10.1054/bjoc.2001.2197
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTIB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTIB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose- and time-dependently and correlated with Her-2/neu overexpression. In addition. incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53. 0 2001 Cancer Research Compaign.
引用
收藏
页码:1764 / 1770
页数:7
相关论文
共 59 条
[1]   Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients [J].
Aas, T ;
Borresen, AL ;
Geisler, S ;
SmithSorensen, B ;
Johnsen, H ;
Varhaug, JE ;
Akslen, LA ;
Lonning, PE .
NATURE MEDICINE, 1996, 2 (07) :811-814
[2]   Bcl-2 inhibits p53 nuclear import following DNA damage [J].
Beham, A ;
Marin, MC ;
Fernandez, A ;
Herrmann, J ;
Brisbay, S ;
Tari, AM ;
LopezBerestein, G ;
Lozano, G ;
Sarkiss, M ;
McDonnell, TJ .
ONCOGENE, 1997, 15 (23) :2767-2772
[3]   COMPLETE SEQUENCING OF THE P53 GENE PROVIDES PROGNOSTIC INFORMATION IN BREAST-CANCER PATIENTS, PARTICULARLY IN RELATION TO ADJUVANT SYSTEMIC THERAPY AND RADIOTHERAPY [J].
BERGH, J ;
NORBERG, T ;
SJOGREN, S ;
LINDGREN, A ;
HOLMBERG, L .
NATURE MEDICINE, 1995, 1 (10) :1029-1034
[4]  
BRACEY TS, 1995, ONCOGENE, V10, P2391
[5]  
Brodowicz T, 1997, INT J CANCER, V73, P875, DOI 10.1002/(SICI)1097-0215(19971210)73:6<875::AID-IJC19>3.0.CO
[6]  
2-3
[7]   Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cells by interferon-α and retinoids [J].
Brodowicz, T ;
Wiltschke, C ;
Kandioler-Eckersberger, D ;
Grunt, TW ;
Rudas, M ;
Schneider, SM ;
Hejna, M ;
Budinsky, A ;
Zielinski, CC .
BRITISH JOURNAL OF CANCER, 1999, 80 (09) :1350-1358
[8]  
Brown JL, 1998, ANIM REPROD SCI, V53, P1
[9]   INDUCTION OF THE GROWTH INHIBITOR IGF-BINDING PROTEIN-3 BY P53 [J].
BUCKBINDER, L ;
TALBOTT, R ;
VELASCOMIGUEL, S ;
TAKENAKA, I ;
FAHA, B ;
SEIZINGER, BR ;
KLEY, N .
NATURE, 1995, 377 (6550) :646-649
[10]   Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer [J].
Burstein, HJ ;
Kuter, I ;
Campos, SM ;
Gelman, RS ;
Tribou, L ;
Parker, LM ;
Manola, J ;
Younger, J ;
Matulonis, U ;
Bunnell, CA ;
Partridge, AH ;
Richardson, PG ;
Clarke, K ;
Shulman, LN ;
Winer, EP .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (10) :2722-2730