Determination of the effect of TGF-β on PSMD4 gene in hepatocellular carcinoma

Proteins that cannot be degraded in the cell are realized by proteolytic pathways. Prosthetic destruction, one of the proteolytic destruction pathways, plays an important role in eukaryotic and prokaryotic cells. The PSMD4 gene, called 26S proteasome non-ATPase subunit 4, is a component of the 26S proteasome. The PSMD4 gene has been expressed in many different tissues. The PSMD4 gene has been proven to be upregulated in hepatocellular carcinoma. At the same time, studies on colon cancer are limited. Within the limited information in the literature, the effects of TGF-β cytokine, known as Transforming Growth Factor, on PSMD4 gene expression in Colon Cancer cell line SW480 and Hepatocellular Carcinoma cell line Hep3B cells were investigated. TGF-β cytokine increased PSMD4 gene expression at mRNA and protein levels in both SW480 and cell line Hep3B cells. In order to determine the signaling pathways, MEKI (MAP2K1), PD169316 (p38b MAPK Inhibitor), Wortmannin (PI3K Inhibitor), NFkB Inhibitor, SP600125 (JNK Inh.), SIS3 (SMAD3) inhibitors were administered with TGF-β. Accordingly, TGF-β administration increases PSMD4 gene expression in Hep3B cells. However, it is understood that none of the examined MAPK, PI3K NFkB and smad pathways are responsible for this increase. Because the activation induced by TGF-β cytokine was reversed only with MEK1 inhibitor. In this case, it is understood that the response of TGF-B on PSMD4 gene expression proceeds through the MAP kinase pathwa