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| Item Type: | Article |
|---|---|
| Title: | YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene |
| Creators Name: | Stein, U., Bergmann, S., Scheffer, G.L., Scheper, R.J., Royer, H.D., Schlag, P.M. and Walther, W. |
| Abstract: | Vaults have been suggested to play a direct role in multidrug resistance (MDR) to anticancer drugs. The human major vault protein (MVP) also known as lung resistance-related protein (LRP) represents the predominant component of vaults that may be involved in the defense against xenobiotics. Here, we demonstrate that besides MDR-related cytostatics, also the non-MDR-related drug 5-fluorouracil (5-FU) was able to induce MVP mRNA and protein expression. Treatment with 5-FU amplified the binding activity and interaction of the transcription factor Y-box binding protein-1 (YB-1) with the Y-box of the human MVP gene promoter in a time-dependent manner. 5-FU also induced reporter expressions driven by a panel of newly generated MVP promoter deletion mutants. Interestingly, stably YB-1 overexpressing cell clones showed enhanced binding of YB-1 to the Y-box motif, associated with enhanced basal as well as 5-FU-inducible MVP promoter-driven reporter expressions. Moreover, transduction of YB-1 cDNA led to increased expression of endogenous MVP protein. Under physiological conditions, we observed a strong coexpression of MVP and YB-1 in human colon carcinoma specimen. In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity. Therefore, YB-1 is directly linked to MVP-mediated drug resistance. |
| Keywords: | 5-Fluorouracil, Drug Resistance, MVP, YB-1 |
| Source: | Oncogene |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Volume: | 24 |
| Number: | 22 |
| Page Range: | 3606-3618 |
| Date: | 1 January 2005 |
| Official Publication: | https://doi.org/10.1038/sj.onc.1208386 |
| PubMed: | View item in PubMed |
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