JAC, a direct target of oncogenic transcription factor Jun, is involved in cell transformation and tumorigenesis

Area of Science:

• Oncogenic transformation
• Gene regulation
• Molecular biology

Background:

• The v-jun oncogene of avian sarcoma virus 17 (ASV17) induces specific cellular changes.
• Understanding genes activated by v-jun is key to deciphering jun-induced cell transformation.

Purpose of the Study:

• To identify and characterize genes specifically activated by the v-jun oncogene.
• To elucidate the role of the identified gene in v-jun-mediated cell transformation and tumorigenesis.

Main Methods:

• Subtractive hybridization to identify differentially expressed genes.
• Doxycycline-controlled conditional cell transformation system for kinetic analysis.
• Nucleotide sequence analysis, transcriptional mapping, and mutational analysis of gene promoters.
• Ectopic expression studies in avian fibroblasts.

Main Results:

• Isolated and identified the JAC gene, specifically activated by v-jun in avian fibroblasts.
• JAC mRNA expression is rapidly induced upon v-jun activation and highly expressed in jun-induced fibrosarcomas.
• The JAC protein shares sequence identity with mammalian keratin-associated proteins, and its promoter contains tandem AP-1 binding sites crucial for synergistic activation by Gag-Jun.
• Ectopic expression of JAC promotes anchorage-independent growth, indicating its role in transformation.

Conclusions:

• The JAC gene is a critical mediator of v-jun-induced cell transformation.
• Deregulation of JAC is an essential event in jun-induced tumorigenesis.
• JAC represents a potential target for understanding and potentially treating cancers driven by v-jun.