Local estrogen formation by Nontumoral, cirrhotic, and malignant human liver tissues and cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2003-08, Vol.63 (16), p.5041-5045
• Main Authors: CASTAGNETTA, Luigi A. M, AGOSTARA, Biagio, MONTALTO, Giuseppe, POLITO, Lucia, CAMPISI, Ildegarda, SAETTA, Annalisa, ITOH, Toru, BIN YU, SHIUAN CHEN, CARRUBA, Giuseppe
• Format: Article
• Language: English
• Subjects: Androgens - metabolism; Aromatase - metabolism; Aromatase Inhibitors; Biological and medical sciences; Carcinoma, Hepatocellular - metabolism; Enzyme Inhibitors - therapeutic use; Estrogens - biosynthesis; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver - metabolism; Liver Cirrhosis - metabolism; Liver Neoplasms - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured; Tumors
• ISSN: 0008-5472; 1538-7445

We have investigated the activity and expression of aromatase enzyme in nontumoral, cirrhotic, and malignant human liver tissues and cells using both chromatographic and reverse transcription (RT)-PCR analyses. After 24- and 72-h incubation of tissue minces or hepatic cell lines with either testosterone or androstenedione as androgen precursor, human hepatocellular carcinoma (HCC) tissues and HepG2 hepatoma cells showed elevated aromatase activity, with estrogen formation rates being 20 and >95%, respectively, as opposed to nontumoral hepatic tissues and nonmalignant Chang liver (CL) cells, where no aromatase activity could be detected. Cirrhotic samples exhibited intermediate enzyme activity. Notably, exposure of HepG2 cells to the aromatase inhibitor Letrozole resulted in a striking decrease of estrogen formation, which became virtually absent at a Letrozole dose of 0.4 nM. RT-PCR analysis revealed markedly lower aromatase mRNA in both CL cells and nontumoral liver tissues, as compared with HepG2 cells and HCC samples. Cirrhotic specimens displayed variable transcript levels, in turn comparable with those observed in nontumoral or HCC tissues. Exon-specific RT-PCR showed prominent expression of exon I.3A-containing message and exon I.4-containing message in CL and HepG2 cells, as in nontumoral and HCC tissues, respectively. The present evidence implies that locally elevated estrogen formation in malignant human liver tissues and cells may have a role in the development and/or maintenance of human HCC, eventually leading to develop alternative strategies for treatment of HCC patients using antiaromatase agents.