title: Expression of wild-type and variant estrogen receptor alpha in liver carcinogenesis and tumor progression.
abstract: 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). In particular, ERα66 was detected in nontumoral and, to a lesser extent, in cirrhotic liver tissues, whereas its expression decreased or became undetectable in HCC tissues and cell lines. The ERα46 splicing variant was detected ubiquitously in all samples; interestingly, however, the ERα36 variant was inversely expressed with respect to ERα66, being highest in HepG2 cells, intermediate in Huh7 cells, and lowest in HA22T cells. It is noteworthy that aromatase was correspondingly expressed with ERα36 and inversely related to ERα66. This observation suggests that a switch from ERα66 to a predominant expression of ERα36 may be associated with development and/or progression of human HCC.
authors.affiliation: Experimental Oncology, Department of Oncology, ARNAS-Civico, Palermo, Italy.
authors.forename: Vitale
authors.initials: V
authors.lastname: Miceli
authors.forename: Letizia
authors.initials: L
authors.lastname: Cocciadiferro
authors.forename: Maria
authors.initials: M
authors.lastname: Fregapane
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zarcone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Polito
authors.forename: Biagio
authors.initials: B
authors.lastname: Agostara
authors.forename: Orazia Maria
authors.initials: OM
authors.lastname: Granata
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carruba
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D001141:Aromatase