Absence of caveolin-1 alters heat shock protein expression in spontaneous mammary tumours driven by Her-2/neu expression

CIOCCA DR; CUELLO-CARRIÓN FD; NATOLI AL; RESTALL C; ANDERSON RA

HISTOCHEMISTRY AND CELL BIOLOGY.

SPRINGER

Año: 2012 vol. 137 p. 187 - 194

0948-6143

In a previous study we measured caveolin-1 protein levels, both in the normal breast and in breast cancer. The study revealed no association between caveolin-1 expression in the epithelial compartment and clinical disease outcome. However, high levels of caveolin-1 in the stromal tissue surrounding the tumor associated strongly with reduced metastasis and improved survival. Using an animal model, we found that the onset of mammary tumors driven by Her-2/neu expression was accelerated in mice lacking caveolin-1. Here we have analysed the heat shock protein (Hsp) response in the tumors of mice lacking stromal caveolin-1. In all cases, the mammary tumors wereestrogen and progesterone receptor negative, and the levels of Her-2/neu (evaluated by immunohistochemistry) were not different between the caveolin-1 +/+ (n=8) and the caveolin-1 -/- (n=7) tumors. However, a significant reduction in the extent of apoptosis was observed in mammary tumors from animals lacking caveolin-1. While Bcl-2, Bax and survivin levels in the tumors were not different, the amount of HSPA (Hsp70) was almost double in the caveolin-1 -/- tumors. In contrast, HSPB1 (Hsp27/Hsp25) levels were significantly lower in the caveolin-1 -/- tumors. The mammary tumors from caveolin-1 null mice expressed more HSPC4 (gp96 or grp94), but HSPC1 (Hsp90), HSPA5 (grp78), HSPD1 (Hsp60) and CHOP were not altered. No significant changes in these proteins were found in the stroma surrounding these tumors. These results demonstrate that the disruption of the Cav-1 gene can cause alterations of specific Hspsas well as tumor development.