.In MMTV-Her-2/neu transgenic mammary tumors the absence of caveolin-1−/− alters PTEN and NHERF1 but not β-catenin expression

CUELLO CARRIÓN FD; CAYADO-GUTIERREZ N; ANTHONY L. NATOLI; CHRISTINA RESTALL; ROBIN L. ANDERSON; SILVINA NADIN; DAIANA ALVAREZ-OLMEDO; GISELA N. CASTRO; FRANCISCO E. GAGO; FANELLI MA; CIOCCA D.R.

CELL STRESS & CHAPERONES.

SPRINGER

Lugar: Berlin; Año: 2013 vol. 787

1355-8145

In a recent study, we have shown that in mammarytumors from mice lacking the Cav-1 gene, there are alterationsin specific heat shock proteins as well as in tumor development.With this in mind, we have now investigated other proteins inthe samemammarymouse tumor model (Her-2/neu expressingmammary tumors from Cav-1 wild type and Cav-1 null mice),to further comprehend the complex tumor-stroma mechanismsinvolved in regulating stress responses during tumor development.In this tumor model the cancer cells always lacked ofCav-1, so the KO influenced the Cav-1 in the stroma. Byimmunohistochemistry, we have found a striking coexpressionof β-catenin and Her-2/neu in the tumor cells.The absence of Cav-1 in the tumor stroma had no effect onexpression or localization of β-catenin and Her-2/neu. Bothproteins appeared co-localized at the cell surface during tumordevelopment and progression. Since Her-2/neu activationinduces MTA1, we next evaluated MTA1 in the mousetumors. Although this protein was found in numerous nuclei,the absence of Cav-1 did not alter its expression level. In contrast, significantly more PTEN protein was noted in the tumors lacking Cav-1 in the stroma, with the protein localized mainly in the nuclei. P-Akt levels were relatively low in tumors from both Cav-1 WT and Cav-1 KO mice. There was also an increase in nuclear NHERF1 expression levels in the tumors arising from Cav-1 KO mice. The data obtained in the MMTV-neu model are consistent with a role for Cav-1in adjacent breast cancer stromal cells in modulating the expression and localization of important proteins implicated in tumor cell behavior.