Identification and characterization of iron homeostasis- related genes and HCC-down-regulated mitochondrial carrier protein (HDMCP), a novel liver-specific uncoupling protein in human hepatocellular carcinoma (HCC)

Abstract

Hepatocellular carcinoma (HCC) is the fourth highest incidence of cancer in men in Singapore. To understand the molecular mechanism of hepatocarcinogenesis, we have examined the variation in gene expression patterns in cancerous and paired non-cancerous liver tissue using cDNA microarrays. The expression of a group of iron homeostasis-related genes, including hepcidin, as well as a novel gene, HCC-down-regulated mitochondrial carrier protein (HDMCP) were significantly and consistently downregulated in HCC. Contrary to the widely held conventional belief that hepatic iron overload is a possible risk factor for hepatocarcinogenesis, our findings suggest that hepatic iron overload detected in HCC patients could be a consequence, and not a cause, of HCC development. On the other hand, overexpression of HDMCP in transiently transfected cells led to the dissipation of mitochondrial membrane potential, indicating that HDMCP might be a long-postulated uncoupling protein in the liver which catalyzes an endogenous mitochondrial proton-conductance pathway.