Premium
Regulation of cell‐to‐cell communication in non‐tumorigenic and malignant human prostate epithelial cells
Author(s) -
Carruba Giuseppe,
Webber Mukta M.,
Quader Salmaan T.A.,
Amoroso Maria,
Cocciadiferro Letizia,
Saladino Francesca,
Trosko James E.,
Castagnetta Luigi A.M.
Publication year - 2002
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10034
Subject(s) - lncap , forskolin , connexin , carcinogenesis , cancer research , intracellular , cell culture , biology , endocrinology , gap junction , cell , prostate , chemistry , medicine , microbiology and biotechnology , cancer , biochemistry , genetics
BACKGROUND Gap‐junction‐mediated intercellular communication (GJIC) is required for normal development and tissue homeostasis. However, the role of GJIC in human prostate carcinogenesis and progression remains ill‐defined. METHODS The ability of hormones, anti‐hormones, and the anti‐hypertensive drug, forskolin, to restore GJIC in non‐tumorigenic (RWPE‐1 and PWR‐1E) and malignant (RWPE‐2, LNCaP, DU‐145) human prostate epithelial cell lines, was examined by Scrape‐Loading/Dye Transfer (SL/DT) and Fluorescence Recovery After Photobleaching (FRAP) methods using an Ultima laser cytometer. RESULTS Results from both assays show that PWR‐1E, RWPE‐2, LNCaP, and DU‐145 cells have weak or absent GJIC activity. However, the non‐tumorigenic RWPE‐1 cells showed restoration of some GJIC (nearly 10%) after 1 hr in the FRAP assay. Forskolin and estrone, which increase intracellular cAMP levels, induced a significant and consistent increase (2.8‐ and 4.4‐fold, respectively) in cell‐to‐cell communication only in the non‐tumorigenic RWPE‐1 cells. Furthermore, estrone induced a two‐fold increase in connexin 43 (Cx43) and a 30% decrease in Cx32 expression, while forskolin caused a 50% reduction in Cx32 with no effect on Cx43 expression in RWPE‐1 cells. CONCLUSIONS These data suggest that agents that increase Cx43:Cx32 ratio may be used to restore GJIC in junctionally‐deficient, non‐tumorigenic immortalized cells, thus providing insights into potential mechanisms responsible for the multistep carcinogenesis in the human prostate. Prostate 50: 73–82, 2002. © 2002 Wiley‐Liss, Inc.