The Tissue-dependent Keratin 19 Gene Transcription Is Regulated by GKLF/KLF4 and Sp1

The study demonstrated that the transcription of the Keratin 19 (K19) gene, which is a marker of stem cells in certain tissues and associated with cancerous transformations, was regulated by the transcription factors GKLF/KLF4 and Sp1. The K19 promoter was active in certain gastrointestinal cancer cells but inactive in other contexts, with its activity linked to a specific region containing binding sites for GKLF/KLF4 and Sp1. GKLF/KLF4 showed a higher binding affinity, especially in cells with low Sp1 levels. Overexpression of these factors in pancreatic acinar cells, which typically do not express K19, led to aberrant expression similar to that seen in pancreatic cancer, highlighting the role of these transcription factors in tissue- and cancer-specific gene expression patterns.