The effect of estradiol on the expression and distribution of CD-MPR in breast cancer cells

BANNOUD N; CARVELLI LF; RUSSO SJ; VARGAS ROIG LM; SOSA MA

ROSARIO

Congreso; SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR; 2014

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR

Cathepsin D (CatD) is involved in the invasion and metastasis of breast cancer cells. This protease is normally transported to lysosomes via mannose-6-phosphate receptors (MPRs). Two types of MPRs have been described to date: the cation-dependent (CD-MPR) and the cation independent (CI-MPR). The CD-MPR could also participate in exocytosis of lysosomal proteins. In mammary carcinomas, CatD is highly secreted as a pro-enzyme, although the mechanism is still poorly understood. Here, we studied the expression and distribution of CatD and CD-MPR in breast tumor cells and a possible hormonal regulation. For this, two breast cancer cell lines were used (MCF-7 and MDA-MB 231, which express or not estrogen, EST, receptors respectively) and compared to normal breast cells (MCF 10A). They were cultured either in the presence or absence of 17β-EST and/or tamoxifen (TX). It was observed that both proteins are highly expressed in MCF-7 cells. In turn, this expression (in MCF-7) was increased in the presence of EST and was reverted by TX. We also observed that CD-MPR is redistributed toward light fractions in a gradient and from a supranuclear location to a more dispersed cytoplasmic signal (by IFI). We concluded that EST could regulate the expression and distribution of CatD and CD-MPR and the interplay of both proteins could be responsible for the high secretion of the enzyme in these cells.