Intercellular communication and human hepatocellular carcinoma

Giuseppe Carruba, Letizia Cocciadiferro, Vincenzo Bellavia, Sergio Rizzo, Christos Tsatsanis, Demetrios Spandidos, Paola Muti, Colin Smith, Parmender P Mehta, Luigi Castagnetta

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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 Huh? 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).

Original languageEnglish (US)
Pages (from-to)202-212
Number of pages11
JournalAnnals of the New York Academy of Sciences
StatePublished - 2004


  • Gap junction-mediated intercellular communication (GJIC)
  • Hepatocellular carcinoma (HCC)
  • Proliferation
  • Steroid
  • Tumor

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science


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