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 journalArticlepeer-review

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 - Jan 22 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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