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Association of gankyrin and stemness factor expression in human colorectal cancer
Hiromasa Mine1, Toshiharu Sakurai, Hiroshi Kashida
1Department of Gastroenterology and Hepatology, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Background:
It is widely accepted that the adenoma-carcinoma sequence represents the process by which most colorectal cancers (CRCs) arise. Although gankyrin is overexpressed in CRC tissues, its roles in the initiation step of colorectal carcinogenesis remain largely unexplored.
Aim:
We investigated the expression of gankyrin and stemness factors in human colorectal adenomas, precancerous lesions, as well as CRC tissues to assess its involvement in colorectal carcinogenesis.
Methods:
Expression of several molecules including gankyrin and certain stemness factors was compared in 50 pairs of adenoma and surrounding normal mucosa using real-time quantitative polymerase chain reaction and in 30 CRC tissues using immunohistochemistry.
Results:
In CRC specimens, expression of CD133, a cancer stem cell marker, was significantly correlated with gankyrin expression. Gankyrin knockdown decreased the expression of vascular endothelial growth factor (VEGF) and stemness factors such as Nanog and Oct-4 in colorectal cancer cells. Expression of gankyrin and these stemness factors was significantly higher in adenomas than in the surrounding normal mucosa. Importantly, a significant correlation was observed between the expression of gankyrin, VEGF, and Nanog in colorectal adenomas.
Conclusion:
In CRC development, gankyrin would control stem cell behavior by regulating the expression of stemness factors.
