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. We have analysed the
heat shock protein (Hsp) response in the
tumors of mice lacking
caveolin-1. In all cases, the mammary
tumors were
estrogen 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 Hsps as well as
tumor development.