Effect of an LH-RH analogue on adhesion molecules in human prostate cancer cells

BACKGROUND. The reduction in or the loss of the cell-cell adhesion often characterizes
epithelial tumor initiation and progression. In the present study, we investigated the
effects of the LH-RH analogue Leuprorelin acetate (LA), alone or associated with Dihydrotestosterone
(DHT), on the expression of the adhesion proteins E-cadherin, α-, β- and
γ-catenin in androgen-sensitive (LNCaP) and -insensitive (PC-3 and DU-145) prostate cancer
cells.
MATERIALS AND METHODS. Protein expression was evaluated by Western blotting on cells treated
for 48 h with LA (10-11 or 10-6 M) and 10-9 M DHT, alone or combined.
RESULTS. In LNCaP cells, all the above mentioned molecules are expressed. PC-3 cells lack
α-catenin, while DU-145 cells only express β- and γ-catenin. In both LNCaP and PC-3 cells
two truncated forms (97 and 35 kDa) of E-cadherin are present other than the functional protein
(120 kDa). In LNCaP cells, no significant changes in E-cadherin (120 and 97 kDa) level
were produced by DHT, while the 35 kDa fragment was reduced by 34%. LA increased the
full length E-cadherin (26-30%) as well as the two fragments (30-49%). The addition of DHT
to LA significantly reduced the analogue-induced E-cadherin raising. In LNCaP cells β- and
γ-catenin were up-regulated either by DHT (24% and 20%, respectively) or LA (up to 18%
and up to 40%, respectively), while the expression of α-catenin was not modified. The combined
DHT/LA treatment results in a less marked increase in β- and γ-catenin levels.
In PC-3 cells no changes in adhesion molecule expression were produced by LA treatment,
while in DU-145 cells the analogue determined an appreciable reduction in β- (20%) and
γ-catenin (up to 35%) levels.
CONCLUSIONS: The up-regulation of E-cadherin, β- and γ-catenin in LNCaP cells by LA may
be considered as another feature of the direct antitumor LH-RH analogue activity, as it may
contribute to the maintenance/restoration of the normal architecture of prostate epithelium.
The LA-induced modifications of catenins in DU-145 cells are worth some further investigations.