D'Assoro Antonino B, Barrett Susan L, Folk Christopher, Negron Vivian C, Boeneman Kelly, Busby Robert, Whitehead Clark, Stivala Franca, Lingle Wilma L, Salisbury Jeffrey L
Tumor Biology Program, Mayo Clinic Foundation, Rochester, MN 55905, USA.
Breast Cancer Res Treat. 2002 Sep;75(1):25-34. doi: 10.1023/a:1016550619925.
Molecular mechanisms leading to genomic instability and phenotypic variation during tumor development and progression are poorly understood. Such instability represents a major problem in the management of breast cancer because of its contribution to more aggressive phenotypes as well as chemoresistance. In this study we analyzed breast carcinomas and tumor-derived cell lines to determine the relationship between centrosome amplification and established prognostic factors. Our results show that centrosome amplification can arise independent of ER or p53 status and is a common feature of aneuploid breast tumors. Centrosome amplification is associated with mitotic spindle abnormalities in breast carcinomas and thus may contribute to genomic instability and the development of more aggressive phenotypes during tumor progression.
在肿瘤发生和发展过程中导致基因组不稳定和表型变异的分子机制仍知之甚少。这种不稳定性是乳腺癌治疗中的一个主要问题,因为它会导致更具侵袭性的表型以及化疗耐药性。在本研究中,我们分析了乳腺癌组织和肿瘤衍生的细胞系,以确定中心体扩增与既定预后因素之间的关系。我们的结果表明,中心体扩增可独立于雌激素受体(ER)或p53状态而出现,并且是非整倍体乳腺肿瘤的一个常见特征。中心体扩增与乳腺癌中的有丝分裂纺锤体异常有关,因此可能在肿瘤进展过程中导致基因组不稳定和更具侵袭性表型的发展。