Major vault protein does not play a role in chemoresistance or drug localization in a non-small cell lung cancer cell line

Kenneth E. Huffman, David R. Corey

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The human major vault protein (MVP) is the primary component of the 13 MDa vault complex. MVP has been implicated in the development of non-P-glycoprotein-mediated drug resistance in cancer cells. Here we present several lines of evidence that dispute this assertion. siRNAs capable of specifically and efficiently knocking down expression of MVP do not alter the ability of resistant cells to remove doxorubicin from the nucleus and do not increase sensitivity to the drug. Conversely, upregulation of MVP in chemosensitive cells does not confer increased drug resistance. In multi-drug resistant (MDR) lung carcinoma cells, fluorescence microscopy reveals that doxorubicin enters the nucleus and is then removed, inconsistent with suggestions that vaults either act to prevent the drug from entering the nucleus or are involved as a nuclear efflux pump. These data suggest that vaults play no direct role in the MDR phenotype in non-small cell lung carcinoma cells and that their cellular function remains unknown. These results also have important implications concerning the value of MVP as a drug target and as a prognostic marker for chemotherapy failure. Our results suggest the need for further investigation into the link between upregulation of vaults and malignancy, the mechanism behind non-P-gp-mediated drug resistance, and the role of vaults in human cells.

Original languageEnglish (US)
Pages (from-to)2253-2261
Number of pages9
JournalBiochemistry
Volume44
Issue number7
DOIs
StatePublished - Feb 22 2005

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Major vault protein does not play a role in chemoresistance or drug localization in a non-small cell lung cancer cell line'. Together they form a unique fingerprint.

  • Cite this