Increased expression of sorcin is associated with multidrug resistance in leukemia cells via up-regulation of MDR1

Nobuyuki Yamagishi1, Ryota Nakao2, Rumi Kondo2

  • 1Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan; Radioisotope Center, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.

Insights

Sorcin protein directly increases multidrug resistance (MDR) in leukemia cells by activating the CREB pathway, which upregulates MDR1/P-glycoprotein (P-gp) expression. This discovery offers new insights into overcoming cancer drug resistance.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Sorcin, a calcium-binding protein, is implicated in multidrug resistance (MDR) phenotypes in various cancer cells.
  • The precise role of sorcin in MDR development requires further elucidation, particularly in leukemia.

Purpose of the Study:

  • To investigate the role of sorcin in the development of MDR in leukemia cells.
  • To identify the molecular mechanisms by which sorcin contributes to MDR.

Main Methods:

  • Correlation analysis between sorcin expression and MDR1/P-glycoprotein (P-gp) expression in leukemia cells.
  • Investigation of sorcin's effect on the mdr1/p-gp gene promoter activity.
  • Assessment of CREB1 phosphorylation and its binding to the mdr1/p-gp promoter.

Main Results:

  • Sorcin expression levels directly correlated with MDR1/P-gp expression.
  • Sorcin induced MDR1/P-gp expression via a cAMP response element (CRE) in the mdr1/p-gp gene promoter.
  • Sorcin overexpression enhanced CREB1 phosphorylation and its binding to the CRE sequence, leading to increased MDR1/P-gp expression.

Conclusions:

  • Sorcin significantly induces MDR1/P-gp expression through the activation of the CREB pathway, contributing to the MDR phenotype in leukemia.
  • Understanding this sorcin-mediated pathway provides potential molecular targets for overcoming MDR in human cancers.

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