Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor and is a potential tumor suppressor in GI cancers. In this study, we have generated two mouse models, Rosa-Cre;Klf4fl/fl and Lgr5-Cre;Klf4fl/fl. KLF4 was deleted by Rosa-Cre in the gastric epithelia cells or by Lgr5-Cre in the antral stem cells in the adult mice. KLF4 deletion resulted in increased proliferating cells and decreased pit mucous cells. Surprisingly, the intestinal goblet cell marker, MUC2, which is not expressed in normal gastric tissues, was strongly induced at the base of the KLF4-deleted antral glands. To understand the clinical relevance of these findings, we analyzed the expression of KLF4 and MUC2 in human gastric cancer. In a subset of human gastric cancer, the expression of KLF4 is negatively associated with MUC2 expression. In conclusion, KLF4 is essential for normal homeostasis of antral stem cells; loss of KLF4 and expression of MUC2 could be important markers for gastric cancer diagnosis.
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The University of Kentucky Biospecimen and Tissue Procurement and Biostatistics and Bioinformatics Shared Resource Facilities are supported by the Markey Cancer Center (P30 CA177558). CL was supported by R01 CA172379 from the NIH. BME was supported by UK SPORE grant (P20 CA 150343) and R01 DK048498.
Yu, Tianxin; Chen, Xi; Lin, T.; Liu, J.; Li, M.; Zhang, W.; Xu, X.; Zhao, W.; Liu, M.; Napier, Dana L.; Wang, Chi; Evers, B. Mark; and Liu, Chunming, "KLF4 Deletion Alters Gastric Cell Lineage and Induces MUC2 Expression" (2016). Markey Cancer Center Faculty Publications. 69.