Aromatase and Amphiregulin Are Correspondingly Expressed in Human Liver Cancer Cells


Address for correspondence: Giuseppe Carruba, M.D., Ph.D., Experimental Oncology Unit, Department of Oncology, M. Ascoli, ARNAS-Civico, Via Carmelo Lazzaro 2, 90127 Palermo, Italy. Voice: +39-091-6664348; fax: +39-091-6664352.


Human hepatocellular carcinoma (HCC) is associated with high mortality rates, being the third most common cause of cancer death worldwide. Although estrogens have been implicated in HCC, their potential role in development and/or progression of this malignancy remains unclear. In this study we investigated mRNA and protein expression of aromatase (Aro) and amphiregulin (AREG) in relation to estrogen receptors (ERs), in HepG2, Huh7, and HA22T human malignant liver cell lines, using RT-PCR and Western blot analyses. Aro expression was significantly higher (∼13-fold, P= 0.003) in HepG2 cells than in Huh7 cells, while no Aro expression could be detected in HA22T cells. Interestingly, the patterns of AREG expression were consistently associated with those of Aro, with ∼3-fold and ∼8-fold higher levels being seen in HepG2 cells than in Huh7 cells (P= 0.002) and HA22T cells (P= 0.0014), respectively. Using a specific set of primers, ERα46 is the only ER variant expressed in all cell lines, while the wild-type ERα66 could not be detected. Western blot analysis revealed a corresponding figure. This evidence suggests that AREG expression may be upregulated by estrogens in human HCC and that locally elevated aromatase activity also may increase malignant cell proliferation through AREG signaling.