WTH3, a new member of the Rab6 gene family, and multidrug resistance

Jidong Shan, Liming Yuan, Daniel R. Budman, Hao Peng Xu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The WTH3 gene was obtained by a DNA fragment isolated by the methylation-sensitive representational difference analysis technique due to its hypermethylation in the human multidrug resistant (MDR) breast cancer cell line MCF7/AdrR. The WTH3 gene product is 89% and 91% identical to the human Rab6 and Rab6c proteins, but possesses an elongated C-terminal region which contains 46 extra amino acids. Nevertheless, we consider the WTH3 gene a new member of the Rab6 gene family. Semi-quantitative reverse transcriptase-polymerase chain reaction results showed that WTH3 was 15 and 4 times downregulated in MCF7/AdrR and MES-SA/Dx5, a human MDR uterine sarcoma cell line, as compared to their non-MDR parental cell lines. Permanent expression of the WTH3 transgene in MDR cell lines increased to varying degrees their sensitivity to several anticancer drugs, which included doxorubicin, taxol, vinblastine, vincristine, and etoposide, as compared to the control sublines transfected with the empty vector. Flow cytometry and fluorescence microscope experiments suggest that the WTH3 transgene stimulated the host's uptake and retention of DOX. Our results imply that the WTH3 gene plays a role(s) in MDR phenotype development in vitro.

Original languageEnglish (US)
Pages (from-to)112-123
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1589
Issue number2
DOIs
StatePublished - Apr 3 2002
Externally publishedYes

Fingerprint

MDR Genes
Cell Line
Genes
Transgenes
Vinblastine
Vincristine
Etoposide
Paclitaxel
Reverse Transcriptase Polymerase Chain Reaction
Sarcoma
Doxorubicin
Methylation
Flow Cytometry
Down-Regulation
Fluorescence
Breast Neoplasms
Phenotype
Amino Acids
DNA
Pharmaceutical Preparations

Keywords

  • Drug resistance
  • G protein
  • Gene transfection
  • Methylation-sensitive representational difference analysis

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

Cite this

WTH3, a new member of the Rab6 gene family, and multidrug resistance. / Shan, Jidong; Yuan, Liming; Budman, Daniel R.; Xu, Hao Peng.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1589, No. 2, 03.04.2002, p. 112-123.

Research output: Contribution to journalArticle

Shan, Jidong ; Yuan, Liming ; Budman, Daniel R. ; Xu, Hao Peng. / WTH3, a new member of the Rab6 gene family, and multidrug resistance. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2002 ; Vol. 1589, No. 2. pp. 112-123.
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