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Functional evidence for Eme1 as a marker of cisplatin resistance
Author(s) -
Tomoda Yoshitaka,
Katsura Mari,
Okajima Miyuki,
Hosoya Noriko,
Kohno Nobuoki,
Miyagawa Kiyoshi
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24268
Subject(s) - cisplatin , ercc1 , biology , cancer research , rad51 , cell culture , chemotherapy , dna repair , genetics , gene , nucleotide excision repair
The ability to predict cisplatin sensitivity in tumors has been expected to greatly improve the outcome of cancer therapy, because the drug is frequently used in a variety of tumors. Although ERCC1 and other repair proteins have been investigated as markers of cisplatin resistance, reliable markers are still needed. Here, we demonstrate that Eme1 levels can predict cisplatin sensitivity more accurately than ERCC1 or Rad51 levels in a variety of human cancer cell lines. Eme1 forms a heterodimeric protein complex with Mus81 and functions as a structure‐specific endonuclease. Haploinsufficiency of Eme1 led to hypersensitivity to cisplatin in the colon cancer cell line HCT116. On the basis of this finding, we examined the relationships between levels of proteins involved in the repair of interstrand cross‐links and cisplatin sensitivity in human tumor cell lines with a variety of origins. Although ERCC1, Rad51 and Mus81 levels correlated with sensitivity to some extent, the clearest correlation was observed with Eme1. Tumors with low Eme1 levels were more sensitive to the drug than tumors with high levels. This suggests that the measurement of Eme1 in tumors may be more informative for cisplatin‐based chemotherapy than that of the currently available markers. © 2009 UICC