The Expression Of Transcription Factor EGR-3 In Hepatocellular Carcinoma

[Background]Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. HCC nearly almost always develops in connection with chronic hepatitis or liver cirrhosis, mainly due to hepatitis B virus or hepatitis C virus infection in China. Every year, 180 000 people die from HCC. However, the incidence of HCC is still increasing. While the molecular mechanisms of the carcinogenesis and progression of HCC have not been clarified.A transcription factor (sometimes called a sequence-specific DNA binding factor) is a protein that binds to specific DNA sequences and thereby controls the transfer (or transcription) of genetic information from DNA to mRNA. Now, researches show that transcription factors (such as NF-Kb, AP-1, HIF, SNAIL, TWIST et al) play important roles in carcinogenesis and progression of carcinoma.Egr family is composed of four members: Egr-1 (NGFI-A, krox24, zif268), Egr-2 (krox20), Egr-3 (PILOT), and Egr-4 (NGFI-C). All of these members share a highly conserved DNA-binding domain composed of three zinc finger motifs that bind and transactivate transcription from the consensus sequence GCG G/T GG GCG. However, the sequences flanking the zinc finger domains are unique to each protein. EGR-1 plays an important role in a series of malignant tumors. Until now, the role of EGR-3 in HCC and its underlying mechanisms are still unknown.[Objectives]To investigate the expression of early growth factor-3(EGR-3) in hepatocellular carcinoma (HCC).[Methods]1. The expression of Egr-3 was analyzed by immunohistochemistry and western blotting in 125 liver caner and adjacent nontumor tissues. The expression of Egr-3 was also analyzed by immunohistochemistry in 5 normal liver tissues;2. Western blot was also applied to confirm the different expression levels of EGR-3 in liver cancer cell lines(HepG2, HepG2.2.15, SMMC7721 and FHCC98).[Results]The expression of EGR-3 in HCC was significantly deregulated in HCC compared with adjacent nontomor liver(P<0.05). The expression of EGR-3 was not associated with patient's gender, age, tumor size and differentiation. EGR-3 was expressed mainly in cytoplasm in HCC, and expressed both in cytoplasm and nucleus in adjacent benign liver tissues and normal liver tissue. The results of western blot in HCC tissues and adjacent nontumor tissues were in accordance with the findings of immunohistochemistry. EGR-3 was detected in four liver cancer cell lines HepG2, HepG2.2.15, SMMC7721 and FHCC98, it expressed at a higher level in HepG2.2.15 cell line than others. To sum up, the present work, for the first time, links EGR-3 with the development of HCC.