Although estrogen receptors (ERs) are expressed in human hepatocellular carcinoma (HCC), several clinical trials have failed to demonstrate the efficacy of antiestrogen treatment in HCC patients. Recently, the identification of several ER splicing variants has enlightened the complex nature of estrogen signaling in peripheral tissues; this may help understanding estrogen role in either nontumoral or malignant nonclassical target organs, including liver. In this work we have investigated mRNA expression of wild-type and splice variants of ERα in nontumoral, cirrhotic, and malignant human liver, as well as in HCC cell lines, using an exon-specific reverse transcription polymerase chain reaction (RT-PCR).
View Article and Find Full Text PDFThere is indirect multiple evidence that hints at a potential role of sex steroids in development and progression of human hepatocellular carcinoma (HCC). In the present study, we have investigated androgen metabolism in a panel of human liver cancer cell lines (HA22T, Huh7, HepG2) and in normal, cirrhotic and malignant human liver tissues aiming to dissect the potential impact of individual enzyme activities and their products in normal and diseased human liver, both in vivo and in vitro. Using our intact cell analysis we were able to assess rates and pathways of androgen metabolism in living conditions.
View Article and Find Full Text PDFIn this study, we investigated androgen metabolism in two different human prostate cancer cell lines, the androgen-responsive LNCaP cells and the nonresponsive PC3 cells. Following 24-h and 72-h incubation with either testosterone (T) or androstenedione (Ad) used as precursor, divergent patterns and rates of androgen metabolism were observed. Given the recent interest in the multiple uses of embryonic and adult stem cells for basic and applied research, we compared the expression of three presumptive stem cell markers (Oct-4, SUZ-12, and Cripto-1), along with connexin 43 (Cx43), Cx32, and androgen receptor (AR), used as cell differentiation gene markers.
View Article and Find Full Text PDFIn this study we investigated the impact of estrogen antagonists and of 16alpha-OHE1 (an estrogen derivative that binds to and induces transactivation of estrogen receptors) on estrogen metabolism in malignant HepG2 human liver cells featured by high estrogen sulfotransferase (EST); our aim was to clarify the potential correlation of EST and ER. As expected, the HepG2 cells exhibited a very high EST activity, with the majority of estrogen metabolites (over 86%) being detected as sulfates by 24 h. The coincubation of E2 and the antiestrogen tamoxifen induced a weak inhibition of EST activity (from 85.
View Article and Find Full Text PDFIn this randomized dietary intervention study (DI) we analyzed levels of androgens, phytoestrogens, and estrogens in 12-h urine samples of 69 healthy postmenopausal women, 37 of whom followed a traditional Mediterranean diet for 6 months (intervention group) as compared to 32 women who followed their regular diet (control group). Circulating levels of both insulin and testosterone (T) were also assayed. Overall, enterolactone (ENL) was the most prominent phytoestrogen in urines of both control and intervention women, and its levels increased by a 20% after DI.
View Article and Find Full Text PDFIn this study we have investigated androgen (testosterone and androstenedione) metabolism in malignant HepG2, Huh-7, and HA22T human liver cell lines. Following 72-h incubation with testosterone or androstenedione, estrogen formation through aromatase activity was consistently higher in HepG2 cells (being nearly 100%) and moderate in Huh7 cells (34%), while it was undetectable in HA22T cells. The produced estrogens are completely conjugated by estrogen sulpho-transferase (EST) in HepG2 cells, while nearly 25% remains in the free form in Huh-7 cells.
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