HMG-I/Y is a c-Jun/activator protein-1 target gene and is necessary for c-Jun-induced anchorage-independent growth in Rat1a cells

Fumihiro Hommura, Motoo Katabami, Virna D. Leaner, Howard Donninger, Takita F. Sumter, Linda Resar, Michael J. Birrer

Research output: Contribution to journalArticle

Abstract

The transcription complex activator protein-1 (AP-1) plays a role In a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1 -responsive target genes, we used a doxycyciine-inducible c-Jun system In Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by c-Jun. Following Induction of c-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of c-Jun expression, and gel mobility shift assays demonstrate that induced c-Jun binds to an AP-1 consensus site at position -1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of c-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing c-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of c-Jun necessary for c-Jun-induced anchorage-independent growth in Rat1a cells.

Original languageEnglish (US)
Pages (from-to)305-314
Number of pages10
JournalMolecular Cancer Research
Volume2
Issue number5
StatePublished - May 1 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Hommura, F., Katabami, M., Leaner, V. D., Donninger, H., Sumter, T. F., Resar, L., & Birrer, M. J. (2004). HMG-I/Y is a c-Jun/activator protein-1 target gene and is necessary for c-Jun-induced anchorage-independent growth in Rat1a cells. Molecular Cancer Research, 2(5), 305-314.