Abstract
The increased expression of β4-galactosyltransferase (β4GalT) 4 is closely associated with poor prognosis of colon cancer. Recently, we showed that the expression of the β4GalT4 gene is regulated by the 0.17 kb core promoter region containing one binding site for Specificity protein 1 (Sp1). To develop a screening method for anti-colon cancer drugs, two sensor cell lines having the luciferase gene under the control of two β4GalT4 gene promoters that differed in length were established from SW480 human colon cancer cells. The hGT4-0.17-sensor cells possessed the luciferase reporter driven by the 0.17 kb promoter, while the hGT4-0.3-sensor cells possessed the luciferase reporter driven by the 0.3 kb promoter containing one binding site each for colon cancer-related transcription factors including activator protein 2, E2F, caudal-related homeobox transcription factors, and Runt-related transcription factors besides Sp1. Upon treatment with mitogen-activated protein kinase signaling inhibitor U0126, the promoter activities of the hGT4-0.3-sensor cells decreased significantly, while those of the hGT4-0.17-sensor cells remained unchanged. These results suggest that the responsiveness to U0126 differs between two sensor cell lines due to the different regulation of the luciferase reporters. This study provides the screening method for anti-colon cancer drugs by the combination of two sensor cell lines.
Highlights
IntroductionBy changing the cell surface glycosylation upon treatment with the inhibitors for glycan biosynthetic pathway such as castanospermine and swainsonine, the metastatic potentials of cancer cells have been shown to decrease [5,6]
Upon malignant transformation, cell surface glycosylation changes drastically [1,2]
Since Specificity protein 1 (Sp1) is well-known transcription factor involved in the regulation of the housekeeping genes [23], it may be hard to discover the drugs that inhibit the expression of the β4GalT4 gene in colon cancer cells by using the core promoter region
Summary
By changing the cell surface glycosylation upon treatment with the inhibitors for glycan biosynthetic pathway such as castanospermine and swainsonine, the metastatic potentials of cancer cells have been shown to decrease [5,6]. Such inhibitors are not specific to the cancer cell types. The findings suggest that if the inhibitors for the expression of the β4GalT genes, which relate to the malignant potentials of specific cancer cell types, are discovered, the inhibitors are useful for cancer therapy. Among the β4GalT family members, the clinical relevance of β4GalT4 was reported that the expression of β4GalT4 increases in Sensors 2018, 18, 2573; doi:10.3390/s18082573 www.mdpi.com/journal/sensors
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