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

BANNOUD N.; CARVELLI L; VARGAS ROIG L.M.; SOSA M.A.

Potrero de los Funes, San Luis

Congreso; Reunión 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 prosaposin (PSAP), and both proteins can be transported together via the receptor sortilin (Sort). Here, we proposed to elucidate the mechanism by which cathepsin D (CatD) is secreted by east cancer 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 17â-estradiol and/or tamoxifen. After treatments, 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 turn, 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 and its receptor, CD-MPR, 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.