As reviewed before, the Sepantronium nmr survivin gene is a potential downstream target for p53 and NF-κB transcriptional regulation buy Ilomastat . Alternatively, the previous finding that bortezomib stabilizes active form of p53 in human LNCaP-Pro5 prostate cancer cells may provide another explanation . Nevertheless, while survivin expression is inhibited by wild type p53 [27–29], survivin and NF-κB appear to be co-expressed in cancer such as in peripheral T-cell lymphoma , and inhibition of NF-κB activity using NF-κB-specific inhibitors decreased survivin expression
. Consistent with these observations, bortezomib resistance requires NF-κB activity in mantle cell lymphoma . Therefore, the potential connection of these factors provide an interesting underlying mechanism, which is likely similar to the mechanism we recently discovered for the p53 and ERα on the survivin gene control in the breast cancer . Finally, the p53 status in RPMI-8226
and Kms11 is not fully consistent in literature. Our literature search indicates that RPMI-8226 has mutant p53 , while Kms11 has wild type p53. However, some publication indicated that Kms11 is p53 null. This is likely due to the hypermethylation of the p53 gene to make p53 expression extremely low . Consistently, BIIB057 our results (Li and Chanan-Khan, unpublished observation) indicated that the expression of p53 in Kms11 was barely detected. Consistent with this, we found that the expression of survivin in Kms11 is comparable with its level in RPMI-8226 (Fig. 3C). Conclusion In conclusion, based on the finding in this study, survivin appears to play a role in bortezomib resistance. The p53 status-associated survivin expression is an important parameter for predicting bortezomib sensitivity, which is largely independent of cancer cell types. Therefore, the finding in this paper should be useful for not only prediction of bortezomib sensitivity, but may also be useful as an essential criterion for bortezomib combination with other anticancer compounds
for treatment of cancer patients. Author information Diane Calinski was a student in the Roswell Park Summer College Student Program at the time for this work. Acknowledgements This work was supported in part by NIH R01 Grants (CA109481, Farnesyltransferase CA133241), a research grant (BCTR63806) from the Susan G. Komen for the Cure Foundation and a research grant from Charlotte Geyer Foundation to FL, and by the NCI Cancer Center Support Grant to the Roswell Park Cancer Institute (CA016056). ACK is a Scholar of the Leukemia and lymphoma Society. References 1. Fujita T, Doihara H, Washio K, Ino H, Murakami M, Naito M, Shimizu N: Antitumor effects and drug interactions of the proteasome inhibitor bortezomib (PS341) in gastric cancer cells. Anticancer Drugs 2007, 18:677–686.PubMedCrossRef 2.