The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1

Keratins play critical roles in cellular differentiation and cytoskeletal o rganization, Keratin 19 (K19) is unique because it has been implicated as a marker of stem cells in some tissues, such as the hair follicle in the ski n. It is also associated with malignant transformation in esophageal and pa ncreatic cancers. Here, we show that the K19 promoter is active in a subset of gastrointestinal cancer cells derived from esophageal and pancreas but inactive in other contexts. This activity was mapped to a short region cont aining an overlapping binding site for gut-enriched Kruppel-like factor (GK LF/KLF4) and Sp1. GKLF has a higher binding affinity and is the predominant binding factor in cells with low Sp-1 protein levels. Pancreatic acinar ce lls normally do not express K19, but overexpression of GKLF and Spl in thes e cells leads to aberrant expression, similar to what is observed in pancre atic cancer. These results demonstrate the functional interaction of ubiqui tous and tissue-restricted transcription factors in determining tissue- and neoplasm-specific patterns of gene expression.