Aberrant expression of cell-cycle regulator cyclin D1 in breast cancer is related to chromosomal genomic instability.

作者: Jia-Chyi Lung , Jan-Show Chu , Jyh-Cherng Yu , Chung-Tai Yue , Yen-Li Lo

DOI: 10.1002/GCC.10072

关键词: GeneticsComparative genomic hybridizationGenome instabilityCyclin EBiologyCyclin DCancer researchCyclin ATumor progressionCyclin D1Chromosome instability

摘要: To account for the accumulation of genomic alterations required tumor progression, it has been suggested that genomes cancer cells are unstable and this instability results from defective mutators (the “mutator phenotype” theory). examine hypothesis abnormal cell-cycle regulators act as contributing to instability, present study, based on primary tissues 71 patients with breast cancer, was performed determine whether there an association between aberrant expression (cyclin A, cyclin D1, E, RB1, p21, p27) chromosomal instability. Comparative hybridization used measure changes, reflecting in individual tumors, whereas immunohistochemistry detect regulators. Overexpression D1 found be significantly correlated increased (defined harboring more than 7 changes), 63% tumors overexpressing 27% not overexpressing, showing (P < 0.05). Interestingly, relationship independent cell outgrowth (as detected by proliferation marker Ki-67) particularly significant expressing p27 or detectable RB1. These suggest plays alternative role regulation stability. © 2002 Wiley-Liss, Inc.

参考文章(45)
R. S. K. Chaganti, J. Houldsworth, Comparative genomic hybridization: an overview. American Journal of Pathology. ,vol. 145, pp. 1253- 1260 ,(1994)
Keith R. Loeb, Lawrence A. Loeb, Genetic Instability and the Mutator Phenotype: Studies in Ulcerative Colitis American Journal of Pathology. ,vol. 154, pp. 1621- 1626 ,(1999) , 10.1016/S0002-9440(10)65415-6
Patrick Meraldi, Jiri Lukas, Andrew M. Fry, Jiri Bartek, Erich A. Nigg, Centrosome duplication in mammalian somatic cells requires E2F and Cdk2-cyclin A. Nature Cell Biology. ,vol. 1, pp. 88- 93 ,(1999) , 10.1038/10054
Christoph Lengauer, Kenneth W. Kinzler, Bert Vogelstein, Genetic instabilities in human cancers Nature. ,vol. 396, pp. 643- 649 ,(1998) , 10.1038/25292
Charles H. Spruck, Kwang-Ai Won, Steven I. Reed, Deregulated cyclin E induces chromosome instability Nature. ,vol. 401, pp. 297- 300 ,(1999) , 10.1038/45836
Lawrence A. Loeb, Cancer cells exhibit a mutator phenotype. Advances in Cancer Research. ,vol. 72, pp. 25- 56 ,(1997) , 10.1016/S0065-230X(08)60699-5
Ping Zhou, I. B. Weinstein, C. M. Weghorst, Wei Jiang, Overexpression of Cyclin D1 Enhances Gene Amplification Cancer Research. ,vol. 56, pp. 36- 39 ,(1996)
François Coulier, Fabienne Kerangueven, Florence Allione, Tetsuro Noguchi, Jocelyne Jacquemier, Hagay Sobol, François Eisinger, Daniel Birnbaum, Véronique Wargniez, Michel Longy, Joelle Simony-Lafontaine, Genome-wide Search for Loss of Heterozygosity Shows Extensive Genetic Diversity of Human Breast Carcinomas Cancer Research. ,vol. 57, pp. 5469- 5474 ,(1997)
A Sgambato, M Begemann, Y Doki, H Yamamoto, E K Han, M Ciaparrone, N Arber, I B Weinstein, P Zhou, Disorders in cell circuitry associated with multistage carcinogenesis: exploitable targets for cancer prevention and therapy. Clinical Cancer Research. ,vol. 3, pp. 2696- 2702 ,(1997)