Regulation of cell-to-cell communication in non-tumorigenic and malignant human prostate epithelial cells.
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.
Carruba
Giuseppe
G
Department of Experimental Oncology and Clinical Application, University of Palermo, Palermo, Italy. lucashbl@unipa.it
Webber
Mukta M
MM
Quader
Salmaan T A
ST
Amoroso
Maria
M
Cocciadiferro
Letizia
L
Saladino
Francesca
F
Trosko
James E
JE
Castagnetta
Luigi A M
LA
D002450:Cell Communication / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D005576:Colforsin / Q000494:pharmacology*; D017630:Connexins / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology; D004970:Estrone / Q000494:pharmacology*; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
D017630:Connexins; D005576:Colforsin; D004970:Estrone