Exogenous expression of WT1 gene influences U937 cell biological behaviors and activates MAPK and JAK-STAT signaling pathways

Leuk Res. 2014 Aug;38(8):931-9. doi: 10.1016/j.leukres.2014.05.006. Epub 2014 May 17.

Abstract

Wilms' tumor 1 (WT1) gene plays important roles in leukemogenesis. To further explore its underlying mechanisms, we transfected two WT1 isoforms, WT1(+17AA/-KTS) and WT1(+17AA/+KTS) into U937, a WT1-null monoblastic cell line, studied their effects on migration, colony formation, apoptosis, gene expression and pertinent signaling pathways of U937 cells. The results showed that WT1(+17AA/-KTS), but not WT1(+17AA/+KTS), enhanced migration and colony forming abilities of U937 cells, and suppressed etoposide-induced U937 cell apoptosis. Transfection of WT1 isoforms activated gene expressions of chemokine, and induced up-regulation of signaling molecules involved in JAK-STAT and MAPK signaling pathways. This study showed that exogenous expression of WT1 gene remarkably affected biological behaviors of U937 cells, and these effects are possibly mediated by up-regulation of genes related to chemokine, JAK-STAT and MAPK signaling pathways.

Keywords: Leukemia; Microarray; Signaling pathway; Target gene; Wilms’ tumor 1 (WT1) gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Movement / genetics*
  • Cell Proliferation*
  • Gene Expression Regulation, Leukemic
  • Humans
  • Janus Kinases / genetics
  • Janus Kinases / metabolism*
  • MAP Kinase Signaling System / genetics*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism*
  • Signal Transduction / genetics
  • Transfection
  • U937 Cells
  • WT1 Proteins / genetics*

Substances

  • STAT Transcription Factors
  • WT1 Proteins
  • WT1 protein, human
  • Janus Kinases