Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

Jeong Eun Park; Seon Rang Woo; Chang Mo Kang; Kyoung Mi Juhn; Yeun Jin Ju; Hyun Jin Shin; Hyun Yoo Joo; Eun Ran Park; In chul Park; Sung Hee Hong; Sang Gu Hwang; Jung Kee Lee; Hae Kwon Kim; Myung Haing Cho; Gil Hong Park; Kee Ho Lee

doi:10.1016/j.bbrc.2010.12.018

Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

Jeong Eun Park, Seon Rang Woo, Chang Mo Kang, Kyoung Mi Juhn, Yeun Jin Ju, Hyun Jin Shin, Hyun Yoo Joo, Eun Ran Park, In chul Park, Sung Hee Hong, Sang Gu Hwang, Jung Kee Lee, Hae Kwon Kim, Myung Haing Cho, Gil Hong Park, Kee Ho Lee

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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.

Original language	English
Pages (from-to)	615-621
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	404
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2010.12.018
Publication status	Published - 2011 Jan 14
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by a grant from the National Nuclear R & D Program and BAERI , the Korean Ministry of Science and Technology . MHC was supported by the National Research Foundation of Korea ( NRF-2010-0000784 ).

Keywords

Chromosomal end-to-end fusion
Multinucleation
Paclitaxel
Telomere

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2010.12.018

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Park, J. E., Woo, S. R., Kang, C. M., Juhn, K. M., Ju, Y. J., Shin, H. J., Joo, H. Y., Park, E. R., Park, I. C., Hong, S. H., Hwang, S. G., Lee, J. K., Kim, H. K., Cho, M. H., Park, G. H., & Lee, K. H. (2011). Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization. Biochemical and biophysical research communications, 404(2), 615-621. https://doi.org/10.1016/j.bbrc.2010.12.018

Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization. / Park, Jeong Eun; Woo, Seon Rang; Kang, Chang Mo et al.
In: Biochemical and biophysical research communications, Vol. 404, No. 2, 14.01.2011, p. 615-621.

Research output: Contribution to journal › Article › peer-review

Park, JE, Woo, SR, Kang, CM, Juhn, KM, Ju, YJ, Shin, HJ, Joo, HY, Park, ER, Park, IC, Hong, SH, Hwang, SG, Lee, JK, Kim, HK, Cho, MH, Park, GH & Lee, KH 2011, 'Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization', Biochemical and biophysical research communications, vol. 404, no. 2, pp. 615-621. https://doi.org/10.1016/j.bbrc.2010.12.018

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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.",

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AU - Juhn, Kyoung Mi

AU - Ju, Yeun Jin

AU - Shin, Hyun Jin

AU - Joo, Hyun Yoo

AU - Park, Eun Ran

AU - Park, In chul

AU - Hong, Sung Hee

AU - Hwang, Sang Gu

AU - Lee, Jung Kee

AU - Kim, Hae Kwon

AU - Cho, Myung Haing

AU - Park, Gil Hong

AU - Lee, Kee Ho

N1 - Funding Information: This work was supported by a grant from the National Nuclear R & D Program and BAERI , the Korean Ministry of Science and Technology . MHC was supported by the National Research Foundation of Korea ( NRF-2010-0000784 ).

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N2 - 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.

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Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

Abstract

Bibliographical note

Keywords

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