title: Intercellular communication and human hepatocellular carcinoma.
abstract: We have previously reported that gap junction-mediated intercellular communication (GJIC) can be restored in junctionally deficient human prostate epithelial cells, also suggesting that GJIC activity is regulated by estrogen. In the present work, we report studies on sex steroid regulation of GJIC and proliferative activity in both nontumoral (Chang liver, CL) and malignant (HepG2, Huh7) human liver cells. Junctional activity and liver cell growth were measured using the scrape-loading/dye-transfer (SL/DT) and the MTS assay, respectively. Using the SL/DT, only Huh7 cells exhibited a moderate degree of junctional activity in basic conditions, while neither CL nor HepG2 cells showed functional GJIC. Under exactly the same experimental approach used for prostate studies, we observed that, once again, both estrogen (either estradiol or estrone) and FK induce a significant increase of GJIC in Huh7 cells, while exposure of HepG2 cells to FK produces only a limited rise of junctional activity in this cell line. However, estrogen induced a significant increase and reduction of the proliferative activity of CL and Huh7 cells, respectively, while growth of HepG2 cells was not affected. While the above evidence suggests that estrogens are primarily implicated in growth regulation and communication of both prostate and liver epithelial cells, it also implies that compounds able to restore GJIC in junctionally deficient cells or prevent its disruption in junctionally proficient cells may be used for development of new strategies in the prevention and/or treatment of several human malignancies, including hepatocellular carcinoma (HCC).
authors.affiliation: Department of Experimental Oncology and Clinical Application, University Medical School, c/o M. Ascoli Cancer Hospital Center, ARNAS-Civico, Via C. Lazzaro 2, 90127 Palermo, Italy. lucashbl@unipa.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carruba
authors.forename: Letizia
authors.initials: L
authors.lastname: Cocciadiferro
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bellavia
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.forename: Christos
authors.initials: C
authors.lastname: Tsatsanis
authors.forename: Demetrios
authors.initials: D
authors.lastname: Spandidos
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.forename: Colin
authors.initials: C
authors.lastname: Smith
authors.forename: Parmender
authors.initials: P
authors.lastname: Mehta
authors.forename: Luigi
authors.initials: L
authors.lastname: Castagnetta
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D009369:Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D011987:Receptors, Steroid / Q000378:metabolism; D013997:Time Factors
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D011987:Receptors, Steroid