The role of T-fimbrin in the response to DNA damage: silencing of T-fimbrin by small interfering RNA sensitizes human liver cancer cells to DNA-damaging agents.
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| Abstract |
Fimbrins (also known as plastins) are actin-binding proteins of the cortical cytoskeleton present in all cells and conserved from yeast to mammals. We previously reported that the up-regulation of T-fimbrin, a fimbrin isoform, in association with G2 arrest following DNA damage and that a lack of T-fimbrin expression shortens the radiation-induced G2 arrest in Chinese hamster ovarian cells. In this study, we further investigated the role of T-fimbrin in DNA-damage response using a panel of human liver cancer cell lines and small interfering RNA technology. T-fimbrin was differentially expressed in human liver cancer cell lines. Colony formation assays revealed that cell lines lacking T-fimbrin expression were highly sensitive to DNA damage compared to cell lines that express T-fimbrin. Using siRNA designed to target T-fimbrin, we demonstrated that silencing endogenous T-fimbrin causes a marked increase in the cellular sensitivity to VP-16 and UV irradiation. Moreover, T-fimbrin deletion abrogated UV-mediated cell cycle checkpoint, and consequently led to increased apoptotic cell death in resistant cells. These findings suggest that the status of T-fimbrin expression may be a useful molecular marker for predicting the responsiveness of cancer cells to treatment with chemotherapeutic drugs.
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| Authors | Hiroshi Ikeda, Yasushi Sasaki, Toshihisa Kobayashi, Hiromu Suzuki, Hiroaki Mita, Minoru Toyota, Fumio Itoh, Yasuhisa Shinomura, Takashi Tokino, Kohzoh Imai |
| Journal | International journal of oncology (Int J Oncol) Vol. 27 Issue 4 Pg. 933-40 (Oct 2005) ISSN: 1019-6439 [Print] Greece |
| PMID | 16142308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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