Laboratory of Oncology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU), Technology and Scientific Center (CCT)-National Research Council of Argentina (CONICET), Ruiz Leal s/n, Parque General San Martín, 5500, Mendoza, Argentina.
Cell Stress Chaperones. 2013 Sep;18(5):559-67. doi: 10.1007/s12192-013-0408-0. Epub 2013 Feb 9.
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 same mammary mouse 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 co-expression of β-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 β-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.
在最近的一项研究中，我们已经表明，在缺乏 Cav-1 基因的小鼠乳腺肿瘤中，存在特定热休克蛋白的改变以及肿瘤的发展。考虑到这一点，我们现在已经在相同的乳腺小鼠肿瘤模型（来自 Cav-1 野生型和 Cav-1 缺失型小鼠的 Her-2/neu 表达乳腺肿瘤）中研究了其他蛋白质，以进一步理解调节肿瘤发展过程中应激反应的复杂肿瘤基质机制。在这个肿瘤模型中，癌细胞总是缺乏 Cav-1，所以 KO 影响了基质中的 Cav-1。通过免疫组织化学，我们发现肿瘤细胞中β-catenin 和 Her-2/neu 的表达明显共表达。肿瘤基质中 Cav-1 的缺失对β-catenin 和 Her-2/neu 的表达或定位没有影响。在肿瘤的发展和进展过程中，这两种蛋白似乎都在细胞表面共定位。由于 Her-2/neu 的激活诱导了 MTA1 的表达，我们接下来评估了 MTA1 在小鼠肿瘤中的表达。尽管这种蛋白在许多核中都有表达，但 Cav-1 的缺失并没有改变其表达水平。相反，在缺乏基质 Cav-1 的肿瘤中，PTEN 蛋白明显增多，主要定位于核内。P-Akt 水平在 Cav-1 WT 和 Cav-1 KO 小鼠的肿瘤中相对较低。在 Cav-1 KO 小鼠的肿瘤中，NHERF1 的核内表达水平也增加了。在 MMTV-neu 模型中获得的数据表明，Cav-1 在调节肿瘤细胞行为相关重要蛋白的表达和定位方面，在邻近的乳腺癌基质细胞中具有重要作用。
