Activating transcription factor 3 is downregulated in hepatocellular carcinoma and functions as a tumor suppressor by regulating cyclin D1

Abstract

ObjectivesTo investigate the expression as well as biological roles of activating transcription factor 3 (ATF3) in human hepatocellular carcinoma (HCC) cells.MethodsReal time PCR and western blot were applied to detect the expression of ATF3 in human HCC specimens. MTT assay was used to analyze cell proliferation after ATF3 was overexpressed. The expression of cyclin D1 was detected by real time PCR in ATF3-silenced/-overexpressed cells and HCC samples. Correlation coefficient was finally analyzed between ATF3 and cyclin D1 in the HCC samples.ResultsThe expression of ATF3 was found to be downregulated in tested HCC specimens. Cellular MTT assays showed that cell proliferation was suppressed in ATF3-overexpressing HepG2 cells. In addition, cyclin D1 gene expression exhibited negative correlation with ATF3 in both cell lines and tissue samples.ConclusionLow expression of ATF3 may function as a tumor suppressor via inhibiting cyclin D1 in HCC.

Master Regulator Activating Transcription Factor 3 (ATF3) in Metabolic Homeostasis and Cancer

“…Overexpression of ATF3 downregulates cyclin D1 expression in HepG2 cells (109). In addition, there was a negative correlation between ATF3 and cyclinD1 mRNA expression in HCC samples (109). ATF3 inhibited cell FIGURE 7 | ATF3 plays an important role in lung cancer.…”

“…ATF3 level is low in human hepatocellular carcinoma (HCC) tissues (108,109), and there was a decreased ATF3 protein level in patients with capsule invasion (108). Li et al had shown that overexpression of ATF3 inhibits growth, decreases cell cycle progression, and increases the apoptotic activity of HepG2 cells (110).…”

“…Li et al had shown that overexpression of ATF3 inhibits growth, decreases cell cycle progression, and increases the apoptotic activity of HepG2 cells (110). Overexpression of ATF3 downregulates cyclin D1 expression in HepG2 cells (109). In addition, there was a negative correlation between ATF3 and cyclinD1 mRNA expression in HCC samples (109).…”

“…Overexpression of ATF3 downregulates cyclin D1 expression in HepG2 cells ( 109 ). In addition, there was a negative correlation between ATF3 and cyclinD1 mRNA expression in HCC samples ( 109 ). ATF3 inhibited cell proliferation in HCC cells, including SK-Hep1, Li-7, MHCC-LM3, and MHCC-97H cells and HCC cell tumorigenesis in vivo ( 111 ).…”