Characterization of Aneuploid Populations with Trisomy 7 and 20 Derived from Diploid Human Colonic Epithelial Cells

作者: Peter Ly , Ugur Eskiocak , Sang B. Kim , Andres I. Roig , Suzie K. Hight

DOI: 10.1593/NEO.101580

关键词:

摘要: Chromosomal instability leading to aneuploidy occurs in most sporadic colorectal cancers (CRCs) and is believed be an early driving force disease progression. Despite this observation, the cellular advantages conferred by these cytogenetic alterations are poorly understood. Here, we provide evidence that serum-free passage of originally diploid, immortalized human colonic epithelial cells (HCECs) gave rise acquisition trisomy 7 (+7), detected more than 40% adenomas. These remain diploid under long-term growth 2% serum conditions. Analysis GTG banding fluorescent situ hybridization no rare preexisting +7 cell original population, suggesting a conversion aneuploid state. The also precedes loss or truncation adenomatosis polyposis coli gene as both express full-length, functional protein. Coculturing fluorescent-labeled demonstrate HCECs have advantage over Defects migration aberrant regulation epidermal factor receptor, located on chromosome 7p, HCECs. Interestingly, knockdown TP53 expression K-RasV12 resulted emergence 20, another nonrandom observed ∼85% CRC. In summary, describe isogenic represent changes occurring frequently characterization 20 may serve unique cell-based models examine effects chromosomal CRC

参考文章(50)
K Aoki, M Aoki, M Sugai, N Harada, H Miyoshi, T Tsukamoto, T Mizoshita, M Tatematsu, H Seno, T Chiba, M Oshima, C-L Hsieh, M M Taketo, Chromosomal instability by β-catenin/TCF transcription in APC or β-catenin mutant cells Oncogene. ,vol. 26, pp. 3511- 3520 ,(2007) , 10.1038/SJ.ONC.1210141
Thomas Ried, Torsten Liersch, Heinz Becker, B. Michael Ghadimi, Marian Grade, Molecular cytogenetics: genomic imbalances in colorectal cancer and their clinical impact. Analytical Cellular Pathology. ,vol. 28, pp. 71- 84 ,(2006) , 10.1155/2006/173815
Bruce M. Boman, Emina Huang, Human Colon Cancer Stem Cells: A New Paradigm in Gastrointestinal Oncology Journal of Clinical Oncology. ,vol. 26, pp. 2828- 2838 ,(2008) , 10.1200/JCO.2008.17.6941
M. A. Nowak, N. L. Komarova, A. Sengupta, P. V. Jallepalli, I.-M. Shih, B. Vogelstein, C. Lengauer, The role of chromosomal instability in tumor initiation. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 16226- 16231 ,(2002) , 10.1073/PNAS.202617399
Norman Pavelka, Giulia Rancati, Jin Zhu, William D. Bradford, Anita Saraf, Laurence Florens, Brian W. Sanderson, Gaye L. Hattem, Rong Li, Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature. ,vol. 468, pp. 321- 325 ,(2010) , 10.1038/NATURE09529
Eduardo M. Torres, Noah Dephoure, Amudha Panneerselvam, Cheryl M. Tucker, Charles A. Whittaker, Steven P. Gygi, Maitreya J. Dunham, Angelika Amon, Identification of aneuploidy-tolerating mutations Cell. ,vol. 143, pp. 71- 83 ,(2010) , 10.1016/J.CELL.2010.08.038
William M. Grady, John M. Carethers, Genomic and Epigenetic Instability in Colorectal Cancer Pathogenesis Gastroenterology. ,vol. 135, pp. 1079- 1099 ,(2008) , 10.1053/J.GASTRO.2008.07.076
Madhvi B. Upender, Jens K. Habermann, Lisa M. McShane, Edward L. Korn, J. Carl Barrett, Michael J. Difilippantonio, Thomas Ried, Chromosome transfer induced aneuploidy results in complex dysregulation of the cellular transcriptome in immortalized and cancer cells. Cancer Research. ,vol. 64, pp. 6941- 6949 ,(2004) , 10.1158/0008-5472.CAN-04-0474
Gianluigi Giannelli, Jutta Falk-Marzillier, Oronzo Schiraldi, William G Stetler-Stevenson, Vito Quaranta, Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science. ,vol. 277, pp. 225- 228 ,(1997) , 10.1126/SCIENCE.277.5323.225
Oliver M. Sieber, Karl Heinimann, Ian P. M. Tomlinson, Genomic instability--the engine of tumorigenesis? Nature Reviews Cancer. ,vol. 3, pp. 701- 708 ,(2003) , 10.1038/NRC1170