Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I - PubMed (original) (raw)
. 2002 Nov 1;11(23):2887-94.
doi: 10.1093/hmg/11.23.2887.
Marie-Anne Debily, Lorène Rozier, Monica Autiero, Alain Billault, Véronique Mayau, Sandrine El Marhomy, John Guardiola, Alain Bernheim, Philippe Coullin, Dominique Piatier-Tonneau, Michelle Debatisse
Affiliations
- PMID: 12393800
- DOI: 10.1093/hmg/11.23.2887
Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I
Marina Ciullo et al. Hum Mol Genet. 2002.
Abstract
Gene amplification plays a critical role in tumor progression. Hence, understanding the factors triggering this process in human cancers is an important concern. Unfortunately, the structures formed at early stages are usually unavailable for study, hampering the identification of the initiating events in tumors. Here, we show that the region containing the PIP gene, which is overexpressed in 80% of primary and metastatic breast cancers, is duplicated in the breast carcinoma cell line T47D. The two copies are organized as a large palindrome, lying 'in loco' on one chromosome 7. Such features constitute the landmark of the breakage-fusion-bridge (BFB) cycle mechanism. In hamster cells selected in vitro to resist cytotoxic drugs, common fragile site (CFS) activation has been shown to trigger this mechanism. Here, we characterize FRA7I at the molecular level and demonstrate that it lies 2 Mb telomeric to the PIP gene and sets the distal end of the repeated sequence. Moreover, our results suggest that the BFB process was frozen within the first cycle by healing of the broken chromosome. T47D cells thus offer a unique opportunity to observe the earliest products of the BFB cycle mechanism. Our findings constitute the first evidence that this amplification mechanism can be initiated in vivo by fragile site activation.
Similar articles
- A role for common fragile site induction in amplification of human oncogenes.
Hellman A, Zlotorynski E, Scherer SW, Cheung J, Vincent JB, Smith DI, Trakhtenbrot L, Kerem B. Hellman A, et al. Cancer Cell. 2002 Feb;1(1):89-97. doi: 10.1016/s1535-6108(02)00017-x. Cancer Cell. 2002. PMID: 12086891 - Chromosome breakage at a major fragile site associated with P-glycoprotein gene amplification in multidrug-resistant CHO cells.
Kuo MT, Vyas RC, Jiang LX, Hittelman WN. Kuo MT, et al. Mol Cell Biol. 1994 Aug;14(8):5202-11. doi: 10.1128/mcb.14.8.5202-5211.1994. Mol Cell Biol. 1994. PMID: 7913517 Free PMC article. - A consistent pattern of RIN1 rearrangements in oral squamous cell carcinoma cell lines supports a breakage-fusion-bridge cycle model for 11q13 amplification.
Shuster MI, Han L, Le Beau MM, Davis E, Sawicki M, Lese CM, Park NH, Colicelli J, Gollin SM. Shuster MI, et al. Genes Chromosomes Cancer. 2000 Jun;28(2):153-63. Genes Chromosomes Cancer. 2000. PMID: 10825000 - Genetic alterations in cancer as a result of breakage at fragile sites.
Popescu NC. Popescu NC. Cancer Lett. 2003 Mar 20;192(1):1-17. doi: 10.1016/s0304-3835(02)00596-7. Cancer Lett. 2003. PMID: 12637148 Review. - Common fragile genes.
Matsuyama A, Croce CM, Huebner K. Matsuyama A, et al. Eur J Histochem. 2004;48(1):29-36. Eur J Histochem. 2004. PMID: 15145773 Review.
Cited by
- Recent insights into the causes and consequences of chromosome mis-segregation.
Devillers R, Dos Santos A, Destombes Q, Laplante M, Elowe S. Devillers R, et al. Oncogene. 2024 Sep 15. doi: 10.1038/s41388-024-03163-5. Online ahead of print. Oncogene. 2024. PMID: 39278989 Review. - DNA fragility at topologically associated domain boundaries is promoted by alternative DNA secondary structure and topoisomerase II activity.
Raimer Young HM, Hou PC, Bartosik AR, Atkin ND, Wang L, Wang Z, Ratan A, Zang C, Wang YH. Raimer Young HM, et al. Nucleic Acids Res. 2024 Apr 24;52(7):3837-3855. doi: 10.1093/nar/gkae164. Nucleic Acids Res. 2024. PMID: 38452213 Free PMC article. - Mechanisms Generating Cancer Genome Complexity: Back to the Future.
Toledo F. Toledo F. Cancers (Basel). 2020 Dec 15;12(12):3783. doi: 10.3390/cancers12123783. Cancers (Basel). 2020. PMID: 33334014 Free PMC article. - Impaired Replication Timing Promotes Tissue-Specific Expression of Common Fragile Sites.
Maccaroni K, Balzano E, Mirimao F, Giunta S, Pelliccia F. Maccaroni K, et al. Genes (Basel). 2020 Mar 19;11(3):326. doi: 10.3390/genes11030326. Genes (Basel). 2020. PMID: 32204553 Free PMC article. - Prolactin-induced protein (PIP)-characterization and role in breast cancer progression.
Urbaniak A, Jablonska K, Podhorska-Okolow M, Ugorski M, Dziegiel P. Urbaniak A, et al. Am J Cancer Res. 2018 Nov 1;8(11):2150-2164. eCollection 2018. Am J Cancer Res. 2018. PMID: 30555735 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous