Absence of stromal Caveolin-1 is an important stressor in spontaneous mammary tumors driven by Her-2/neu.

F. DARIO CUELLO-CARRION; NIUBYS CAYADO GUTIERREZ; ANTHONY L. NATOLI; CHRISTINA RESTALL; ROBIN ANDERSON; DANIEL R. CIOCCA

Porto Alegre

Workshop; Workshop Cell Stress. Cell Stress Society International; 2012

Cell Stress Society International

A drastic reduction in the extent of apoptosis was observed in the tumors from mice lacking Cav-1. Bcl-2 was not detected in the tumors and Bax and Survivin were not differentially expressed. In contrast, HSPA (Hsp70 detected by mouse MAb BRM-22) tumor levels were almost double in the Cav-1 -/- animals. On the other hand, HSPB1 (Hsp25/27) tumor levels were significantly lower in the Cav-1 -/- mice. The tumors from mice lacking of Cav-1 showed higher HSPC4 (Gp96 or Grp94), but no differences in HSPC1 (Hsp90), HSPA5 (Grp78) or HSPD1 (Hsp60). PTEN nuclear levels were significantly higher in tumors arising in the Cav-1 null mice while p-Akt levels did not change significantly. MTA-1 and ƒÒ-Catenin levels were not changed. In all cases ƒÒ- catenin was localised to the cell membrane. In comparison, in Her-2/neu positive human breast cancer, exclusive ƒÒ-Catenin localisation was associated with enhanced disease free survival.The presence of Cav-1 in the tumor microenvironment modulates the response of specific HSPs, PTEN and tumor development.