KLF4 deletion alters gastric cell lineage and induces MUC2 expression.
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;Klf4(fl/fl) and Lgr5-Cre;Klf4(fl/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.
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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Yu
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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Chen
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.|Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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Lin
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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J
Liu
Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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Li
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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Zhang
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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Xu
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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Zhao
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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Liu
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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Napier
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
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Wang
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.|Department of Surgery, University of Kentucky, Lexington, KY 40506, USA.
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Evers
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.|Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40506, USA.
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Liu
D000375:Aging / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D019426:Integrases / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D055262:Mucin-2 / Q000378:metabolism*; D011706:Pyloric Antrum / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013270:Stomach / Q000166:cytology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C493597:Lgr5 protein, mouse; D055262:Mucin-2; D043562:Receptors, G-Protein-Coupled; C045073:Cre recombinase; D019426:Integrases