| First Author | Claij N | Year | 2004 |
| Journal | Oncogene | Volume | 23 |
| Issue | 1 | Pages | 260-6 |
| PubMed ID | 14712231 | Mgi Jnum | J:339372 |
| Mgi Id | MGI:7519288 | Doi | 10.1038/sj.onc.1207015 |
| Citation | Claij N, et al. (2004) Msh2 deficiency does not contribute to cisplatin resistance in mouse embryonic stem cells. Oncogene 23(1):260-6 |
| abstractText | Several reports have suggested that a defect in the DNA mismatch repair (MMR) system not only causes resistance to methylating agents but also confers low-level resistance to the chemotherapeutic drug cisplatin. Here we report that in a clonogenic assay, mouse embryonic stem (ES) cells deficient for the MMR protein MSH2 respond similarly as wild-type cells to cisplatin. Furthermore, restoring MSH2 expression in a cisplatin-resistant subclone selected from an Msh2(-/-) cell population did not sensitize cells to cisplatin. To ascertain that our observations were not the result of a mutation in the Msh2(-/-) cells that obscured the contribution of a defective MMR machinery to cisplatin resistance, we made use of the Cre-lox system to create a cell line in which the Msh2 gene can be conditionally inactivated. However, while de novo inactivation of Msh2 rendered cells tolerant to the methylating drug N-methyl-N'-nitro-N-nitrosoguanidine as expected, it did not alter the sensitivity to cisplatin. In addition, we were not able to derive cisplatin-resistant subclones from this freshly generated MMR-deficient cell line. Thus, in ES cells we did not find evidence for direct involvement of MMR deficiency in cisplatin resistance. |
