STAT3 and MITF cooperatively induce cellular transformation through upregulation of c-fos expression

Akiko Joo, Hiroyuki Aburatani, Eiichi Morii, Hideo Iba, Akihiko Yoshimura

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The signal transducer and activator of transcription (STAT) family proteins are transcription factors critical in mediating cytokine signaling. Among them, STAT3 is frequently activated in a number of human cancers and transformed cell lines and is implicated in tumorigenesis. However, although constitutively activated STAT3 mutant (STAT3C) leads to cellular transformation, its transformation potential such as colony-forming activity in soft-agar is much weaker than that of v-src. To identify tumorigenic factors that cooperatively induce cellular transformation with STAT3C, we screened the retroviral cDNA library. We found that the microphthalmia-associated transcription factor (MITF), an essential transcription factor for melanocyte development and pigmentation, induces anchorage-independent growth of NIH-3T3 cells in cooperation with STAT3C. Microarray analysis revealed that c-fos is highly expressed in transformants expressing STAT3C and MITF. Promoter analysis and chromatin immunoprecipitation assay suggested that both STAT3 and MITF can cooperatively upregulate the c-fos gene. In addition, the transformation of NIH-3T3 cells by both MITF and STAT3C was significantly suppressed by a dominant-negative AP-1 retrovirus. These data indicate that MITF and STAT3 cooperatively induce c-fos, resulting in cellular transformation.

Original languageEnglish
Pages (from-to)726-734
Number of pages9
JournalOncogene
Volume23
Issue number3
DOIs
Publication statusPublished - 2004 Jan 22
Externally publishedYes

Keywords

  • Cellular transformation
  • MITF
  • STAT3
  • c-fos

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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