Analysis of Gene Expression Patterns and Chromosomal Changes Associated with Aging

作者: Jochen B. Geigl , Sabine Langer , Simone Barwisch , Katrin Pfleghaar , Gaby Lederer

DOI: 10.1158/0008-5472.CAN-04-2151

关键词:

摘要: Age is the largest single risk factor for development of cancer in mammals. Age-associated chromosomal changes, such as aneuploidy and telomere erosion, may be vitally involved initial steps tumorigenesis. However, changes gene expression specific increased with age have not yet been characterized. Here, we address these questions by using a panel fibroblast cell lines lymphocyte cultures from young old groups. Oligonucleotide microarrays were used to characterize 14,500 genes. We measured length analyzed chromosome copy number structural rearrangements multicolor interphase fluorescence situ hybridization 7-fluorochrome multiplex hybridization, tried show relationship between patterns changes. These analyses revealed genes both cycle proliferation that are differently expressed aged cells. More importantly, our data an association age-related level centromere kinetochore function microtubule spindle assembly apparatus. To verify some also tumorigenesis, compared chromosomally stable microsatellite instability unstable colorectal tumor lines. Three (Notch2, H2AFY2, CDC5L) showed similar differences observed suggesting they play role

参考文章(63)
Loren S Michel, Vasco Liberal, Anupam Chatterjee, Regina Kirchwegger, Boris Pasche, William Gerald, Max Dobles, Peter K Sorger, VVVS Murty, Robert Benezra, None, MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells Nature. ,vol. 409, pp. 355- 359 ,(2001) , 10.1038/35053094
Celina G. Kleer, Kenneth L. van Golen, Yanhong Zhang, Zhi-Fen Wu, Mark A. Rubin, Sofia D. Merajver, Characterization of RhoC expression in benign and malignant breast disease: A potential new marker for small breast carcinomas with metastatic ability American Journal of Pathology. ,vol. 160, pp. 579- 584 ,(2002) , 10.1016/S0002-9440(10)64877-8
Ronald A. DePinho, The age of cancer Nature. ,vol. 408, pp. 248- 254 ,(2000) , 10.1038/35041694
Vincent J Cristofalo, A DNA chip off the aging block Nature Medicine. ,vol. 6, pp. 507- 507 ,(2000) , 10.1038/74983
Nancy Joste, William A. Palmisano, Steven A. Belinsky, Minoru Toyota, Manel Esteller, Sally A. Winters, Stephen B. Baylin, Marcie J. Grimes, Kevin P. Crume, Aberrant promoter methylation of the transcription factor genes PAX5 alpha and beta in human cancers. Cancer Research. ,vol. 63, pp. 4620- 4625 ,(2003)
Steven E. Artandi, Sandy Chang, Shwu-Luan Lee, Scott Alson, Geoffrey J. Gottlieb, Lynda Chin, Ronald A. DePinho, Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice Nature. ,vol. 406, pp. 641- 645 ,(2000) , 10.1038/35020592
Xinsheng Nan, Huck-Hui Ng, Colin A. Johnson, Carol D. Laherty, Bryan M. Turner, Robert N. Eisenman, Adrian Bird, Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex Nature. ,vol. 393, pp. 386- 389 ,(1998) , 10.1038/30764
W. D. Fixsen, Min Han, H. R. Horvitz, C. J. Malone, UNC-84 localizes to the nuclear envelope and is required for nuclear migration and anchoring during C. elegans development. Development. ,vol. 126, pp. 3171- 3181 ,(1999) , 10.1242/DEV.126.14.3171
D. H. Ly, Mitotic misregulation and human aging. Science. ,vol. 287, pp. 2486- 2492 ,(2000) , 10.1126/SCIENCE.287.5462.2486
Karl Lenhard Rudolph, Sandy Chang, Han-Woong Lee, Maria Blasco, Geoffrey J Gottlieb, Carol Greider, Ronald A DePinho, None, Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell. ,vol. 96, pp. 701- 712 ,(1999) , 10.1016/S0092-8674(00)80580-2