Secretory Leukocyte Protease Inhibitor expression disrupts epithelial cadherin adherent complex, induces beta-catenin re-localization and triggers apoptosis in breast tumor cells

ROSSO M; LAPYCKYJ L; AMIANO N; BESSO MJ; SANCHEZ M; CHULUYAN E; VAZQUEZ M

Liverpool

Congreso; 18th International Meeting of the European Society of Gynaecological Oncology (ESGO); 2013

Abstract: Objectives Epithelial cadherin (Ecad) is a transmembrane glycoprotein involved in cell-cell adhesion through its extracellular domain, whereas the intracellular domain strengthens binding via interactions with B-catenin and the actin cytoskeleton. Ecad protects mammary epithelial cells from apoptosis and its loss has been well documented during breast tumor progression. Secreted serine-protease inhibitors, such as SLPI (Secretory Leukocyte Protease Inhibitor), have both anti- and pro-tumorigenic activities. Particularly in breast cancer, low and high levels of SLPI have been detected and related to tumor regression and progression. Using an in vivo model, SLPI expression was reported to decrease mammary tumor growth and to induce apoptosis-related changes. Notwithstanding its relevance, there are no reports on how changes in SLPI expression in tumor cells affect Ecad and other members of the adherent complex. Aim:To evaluate the effect of SLPI upon Ecad expression and proteins related to it in human (MCF-7) and murine (F3II) breast cancer in vitro models. Methods mRNA: standard/real-time PCR, protein: WIB/immunocytochemistry. Results SLPI expression was associated to decreased mRNA/protein Ecad levels. Moreover, it caused disruption of the Ecad-B-catenin complex, changing the balance of pro- and anti-apoptotic proteins (Bax/Bcl2), and eventually leading to apoptosis (TUNEL). This process was, at least in part, mediated by nuclear B-catenin and changes in protein expression associated to its re-localization (cMyc, cyclin D1). Conclusions The pro-apoptotic B-catenin effect induced by SLPI expression may have great impact in breast cancer treatment, given the potential therapeutic use of SLPI in this disease and the relevance of Ecad functionality in breast tumor progression.