Possible hormonal regulation of the traffic and secretion of proteases in breast cancer cells.

BANNOUD N; CARVELLI L; VARGAS-ROIG L; SOSA MA

San Luis

Congreso; XXX Reunión Anual de la Sociedad de Biología de Cuyo.; 2012

Sociedad de Biología de Cuyo

Evidence have demonstrated that lysosomal proteases, as cathepsins, are secreted by tumoral cells, and they may play a role in tumor progression. In most cell types, these enzymes are transported to lysosomes via mannose-6-phosphate receptors (MPRs), sortilin or other alternative mechanisms. Two forms of MPRs have been described so far; the cation-dependent (CD-MPR) and the cation-independent (CI-MPR) MPR. The CD-MPR could participate additionally in the secretion of lysosomal enzymes. In some cell types, pro-cathepsin D (pro-CatD) interacts with the lysosomal precursor prosaposin (PSAP), and both proteins can be transported together to lysosomes or they can be released to the medium, via the receptor sortilin (Sort). In tumoral cells it has been demonstrated that pro-CatD is transported to lysosomes by a mechanism independent of MPRs, although the regulation of this transport is still controversial. Here, we proposed to elucidate the mechanism by which the cathepsins are secreted by breast tumoral cells,, and if it is regulated by hormones. We studied the expression of Cat D, PSAP, CD-MPR and Sort in two cell lines (MCF-7 and MDA-MB231), in the presence or absence of 17β-estradiol and/or antagonists. The cells were cultured and treated with the hormone and/or with tamoxifen (TMX) for 72 h. Proteins from cell lysates were subjected to electrophoresis and analysed by immunoblot. It was observed that expression of CatD, CD-MPR and PSAP in MCF-7 is higher than in MDA-MB231 cells. In turrn, estradiol induced an increase in the expression of CatD and CD-MPR in MCF-7 cells, and this effect was reversed by tamoxifen. From these preliminary results we suggest that expression of Cat D, CD-MPR and PSAP is influenced by estradiol and the differences observed between both cell lines may be due to the presence of estradiol receptors in MCF-7 cells.