P-cadherin and b-catenin are useful prognostic markers in breast cancer patients; b-catenin interacts with heat shock protein Hsp27.

FANELLI MA,; MONTT-GUEVARA M; DIBLASI AM; GAGO FE; TELLO O; CUELLO-CARRIóN FD; CALLEGARI E; BAUSERO MA; CIOCCA DR

CELL STRESS & CHAPERONES.

SPRINGER

Año: 2008 p. 207 - 220

1355-8145

The cadherin-catenin proteins have in common with heat shock proteins (HSP), the capacity to bind/interact proteins of other classes. Moreover, there are common molecular pathways that connect the HSP response and the cadherin-catenin protein system. In the present study, we have explored whether in breast cancer the HSP might interact functionally with the cadherin-catenin cell adhesion system. b-catenin was immunoprecipitated (IP) from breast cancer biopsy samples and the protein complexes isolated in this way were probed with antibodies against HSP family members. We are thus the first to demonstrate a specific interaction between b-catenin and Hsp27. However, b-catenin did not bind Hsp60, Hsp70, Hsp90, gp96 or the ER stress response protein CHOP. To confirm the finding of Hsp27-b-catenin interaction, the 27 kDa immunoprecipitated band was excised from one dimensional PAGE gels and submitted to LC-ESI-MSMS, confirming a role for Hsp27. In addition, b-catenin interacted with other proteins including HSF1 (heat shock transcription factor 1), P-cadherin and caveolin-1. In human breast cancer biopsy samples, b-catenin was co-expressed in the same tumor areas and in the same tumor cells that expressed Hsp27. However, this co-expression was strong when b-catenin was present in the cytoplasm of the tumor cells, not when b-catenin was expressed at the cell surface only. Furthermore, murine breast cancer cells transfected with hsp25 showed a redistribution of b-catenin from the cell membrane to the cytoplasm. When the prognostic significance of cadherin-catenin expression was examined by immunohistochemistry in breast cancer patients (n=215, follow-up: >10 years) we found that the DFS and OS were significantly shorter for patients expressing P-cadherin and for patients showing expression of b-catenin in the cytoplasm only (not at the cell surface). The interactions of b-catenin with Hsp27 and with HSF1 may explain some of the molecular pathways that influence tumor cell survival and the clinical significance in the prognosis of the breast cancer patients.