TY - JOUR
T1 - Intercellular communication and human hepatocellular carcinoma
AU - Carruba, Giuseppe
AU - Cocciadiferro, Letizia
AU - Bellavia, Vincenzo
AU - Rizzo, Sergio
AU - Tsatsanis, Christos
AU - Spandidos, Demetrios
AU - Muti, Paola
AU - Smith, Colin
AU - Mehta, Parmender P
AU - Castagnetta, Luigi
PY - 2004
Y1 - 2004
N2 - 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).
AB - 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).
KW - Gap junction-mediated intercellular communication (GJIC)
KW - Hepatocellular carcinoma (HCC)
KW - Proliferation
KW - Steroid
KW - Tumor
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U2 - 10.1196/annals.1322.025
DO - 10.1196/annals.1322.025
M3 - Article
C2 - 15650246
AN - SCOPUS:20144363441
SN - 0077-8923
VL - 1028
SP - 202
EP - 212
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -