Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization
- Authors
- Park, Jeong-Eun; Woo, Seon Rang; Kang, Chang-Mo; Juhn, Kyoung-Mi; Ju, Yeun-Jin; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun Ran; Park, In-chul; Hong, Sung Hee; Hwang, Sang-Gu; Lee, Jung-Kee; Kim, Hae Kwon; Cho, Myung-Haing; Park, Gil Hong; Lee, Kee-Ho
- Issue Date
- 14-1월-2011
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Telomere; Paclitaxel; Chromosomal end-to-end fusion; Multinucleation
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.404, no.2, pp.615 - 621
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 404
- Number
- 2
- Start Page
- 615
- End Page
- 621
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/113274
- DOI
- 10.1016/j.bbrc.2010.12.018
- ISSN
- 0006-291X
- Abstract
- The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop. (C) 2010 Elsevier Inc. All rights reserved.
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