The c-Jun-induced transformation process involves complex regulation of tenascin-C expression

Area of Science:

• Molecular Biology
• Cell Biology
• Oncology

Background:

• The transcription factor c-Jun, activated by the ras oncogene, is known to transform cells.
• While c-Jun's activation pathways are studied, its cellular targets remain largely unknown.
• Extracellular matrix proteins play roles in cell attachment, migration, and growth control.

Purpose of the Study:

• To identify cellular targets of c-Jun.
• To investigate the role of tenascin-C in c-Jun-mediated cellular effects.
• To elucidate the transcriptional regulation of tenascin-C by c-Jun.

Main Methods:

• Differential screening of a cDNA library from rat embryo fibroblasts (REF).
• Transient and stable overexpression of c-Jun in REF and FR3T3 cells.
• Reporter construct assays using the tenascin-C promoter (-220 to +79).
• Gel shift experiments and co-transfection assays.

Main Results:

• Tenascin-C was identified as a c-Jun-upregulated gene.
• Transient c-Jun overexpression induced tenascin-C expression, while stable transformation repressed it.
• c-Jun-induced tenascin-C activation involved AP-1 and NF-kappaB binding sites (-146 and -210, respectively).
• c-Jun and NF-kappaB synergistically transactivated the tenascin-C promoter.

Conclusions:

• The extracellular matrix protein tenascin-C is a novel target of the transcription factor c-Jun.
• The regulation of extracellular matrix composition is implicated in c-Jun-induced cell transformation.
• Tenascin-C expression is differentially regulated by transient versus stable c-Jun activity.