Correlation between centrosome abnormalities and chromosomal instability in human pancreatic cancer cells

被引:90
作者
Sato, N [1 ]
Mizumoto, K [1 ]
Nakamura, M [1 ]
Maehara, N [1 ]
Minamishima, YA [1 ]
Nishio, S [1 ]
Nagai, E [1 ]
Tanaka, M [1 ]
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Fukuoka 8128582, Japan
关键词
D O I
10.1016/S0165-4608(00)00384-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chromosomal instability, characterized by abnormal numbers or structures of chromosomes, is a common feature of human cancers, but the mechanisms behind these changes are still unclear. Since centrosomes play a pivotal role in balanced chromosomal segregation during mitosis, we attempted to investigate the association between centrosorne abnormalities and chromosomal instability in a large number of human pancreatic cancer cell lines. Immunofluorescence microscopy revealed centrosomes that were highly atypical with respect to their size, shape, and number in most cell lines. These abnormal centrosomes contributed to the assembly of multipolar spindles, resulting in defective mitosis and chromosome mis-segregation. Interestingly, a high frequency of centrosome defects inversely correlated with the growth rate of cells in culture. Fluorescence in situ hybridization revealed a dramatic variation of chromosome numbers in cell lines with the defective centrosome phenotype. Furthermore, a significant positive correlation existed between the level of centrosome defects and the level of chromosomal imbalances. These results indicate that centrosome abnormalities can lead to spindle disorganization and chromosome segregation errors, which may drive the accumulation of chromosomal alterations. Thus. defects in centrosome function ma!: be an underlying cause of genetic instability in human pancreatic cancers. (C) 2001 Elsevier Science Inc. All rights reserved.
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页码:13 / 19
页数:7
相关论文
共 35 条
[1]   KARYOTYPIC ABNORMALITIES IN TUMORS OF THE PANCREAS [J].
BARDI, G ;
JOHANSSON, B ;
PANDIS, N ;
MANDAHL, N ;
BAKJENSEN, E ;
ANDRENSANDBERG, A ;
MITELMAN, F ;
HEIM, S .
BRITISH JOURNAL OF CANCER, 1993, 67 (05) :1106-1112
[2]  
Brinkley BR, 1998, CELL MOTIL CYTOSKEL, V41, P281, DOI 10.1002/(SICI)1097-0169(1998)41:4<281::AID-CM1>3.0.CO
[3]  
2-C
[4]  
BRINKLEY BR, 1995, ANN REV CELL BIOL, V1, P145
[5]   Mutations of mitotic checkpoint genes in human cancers [J].
Cahill, DP ;
Lengauer, C ;
Yu, J ;
Riggins, GJ ;
Willson, JKV ;
Markowitz, SD ;
Kinzler, KW ;
Vogelstein, B .
NATURE, 1998, 392 (6673) :300-303
[6]   Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression [J].
Carroll, PE ;
Okuda, M ;
Horn, HF ;
Biddinger, P ;
Stambrook, PJ ;
Gleich, LL ;
Li, YQ ;
Tarapore, P ;
Fukasawa, K .
ONCOGENE, 1999, 18 (11) :1935-1944
[7]   Pericentrin and γ-tubulin form a protein complex and are organized into a novel lattice at the centrosome [J].
Dictenberg, JB ;
Zimmerman, W ;
Sparks, CA ;
Young, A ;
Vidair, C ;
Zheng, YX ;
Carrington, W ;
Fay, FS ;
Doxsey, SJ .
JOURNAL OF CELL BIOLOGY, 1998, 141 (01) :163-174
[8]   PERICENTRIN, A HIGHLY CONSERVED CENTROSOME PROTEIN INVOLVED IN MICROTUBULE ORGANIZATION [J].
DOXSEY, SJ ;
STEIN, P ;
EVANS, L ;
CALARCO, PD ;
KIRSCHNER, M .
CELL, 1994, 76 (04) :639-650
[9]   Abnormal centrosome amplification in the absence of p53 [J].
Fukasawa, K ;
Choi, T ;
Kuriyama, R ;
Rulong, S ;
VandeVoude, GF .
SCIENCE, 1996, 271 (5256) :1744-1747
[10]  
Ghadimi BM, 2000, GENE CHROMOSOME CANC, V27, P183, DOI 10.1002/(SICI)1098-2264(200002)27:2<183::AID-GCC10>3.3.CO