In MMTV-Her-2/neu transgenic mammary tumors the absence of caveolin-1 (-/-) alters PTEN and NHERF1 but not beta-catenin expression

F. DARÍO CUELLO-CARRION; NIUBYS CAYADO-GUTIÉRREZ; ANTHONY L. NATOLI; CHRISTINA RESTALL; ROBIN L. ANDERSON; SILVINA NADIN; DAIANA ALVAREZ OLMEDO; GISELA N. CASTRO; FRANCISCO E. GAGO; MARIEL A. FANELLI; DANIEL R. CIOCCA

CELL STRESS & CHAPERONES.

SPRINGER

Lugar: Berlin; Año: 2013 vol. 18 p. 559 - 567

1355-8145

In a recent study, we have shown that in mammary tumors from mice lacking the Cav-1 gene, there are alterations in specific heat shock proteins as well as in tumor development. With this in mind, we have now investigated other proteins in the samemammarymouse tumor model (Her-2/neu expressing mammary tumors from Cav-1 wild type and Cav-1 null mice), to further comprehend the complex tumor-stroma mechanisms involved in regulating stress responses during tumor development. In this tumor model the cancer cells always lacked of Cav-1, so the KO influenced the Cav-1 in the stroma. By immunohistochemistry, we have found a striking coexpression of beta-catenin and Her-2/neu in the tumor cells. The absence of Cav-1 in the tumor stroma had no effect on expression or localization of beta-catenin and Her-2/neu. Both proteins appeared co-localized at the cell surface during tumor development and progression. Since Her-2/neu activation induces MTA1, we next evaluated MTA1 in the mouse tumors. 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-1 in adjacent breast cancer stromal cells in modulating the expression and localization of important proteins implicated in tumor cell behavior.