Abstract
Estrogens play important roles in the growth and invasion of estrogen-dependent human neoplasms. Aromatase overexpression has been reported to be expressed in hepatitis and hepatocellular carcinoma (HCC) compared to normal liver but its details in these hepatic diseases have remained unclear. Therefore in this study, we immunolocalized aromatase using immunohistochemistry in patients with liver cirrhosis, steatosis, hepatitis, HCC, and metastasis liver carcinoma (MLC) in order to study intrahepatic aromatase in details. Aromatase immunoreactivity was predominantly expressed in non-neoplastic hepatocytes around tumor cells. We then evaluated the effects of an interaction between hepatocytes and carcinoma cells on expression of aromatase mRNA in HepG2 using a co-culture systems. Aromatase mRNA levels in HepG2 were significantly increased by co-cultivation with all carcinoma cell lines examined. The same exon 1 splicing variant was used in aromatase expression in HepG2 cells regardless of carcinoma cell lines employed in the co-culture system. These findings all indicated that carcinoma cells, whether metastatic or primary, induced aromatase expression in adjacent normal hepatocytes through the soluble aromatase inducible factors in hepatic microenvironments.
