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

Abstract

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.