Beta catenin interacts with heat shock protein hsp27 and heat shock transcription factor 1 and it is a useful prognostic marker in breast cancer patients

FE GAGO; MA FANELLI; MM MONTT GUEVARA; AM DIBLASSI; O TELLO; FD CUELLO-CARRIÓN; E CALLEGARI; DR CIOCCA

Chicago

Congreso; 43rd Annual Meeting of the American Society of Clinical Oncology; 2007

We have explored whether in breast cancer heat shock proteins (Hsps) might interact with proteins involved with the cadherin-catenin cell adhesion system, which have important roles in signaling pathways and tumor cell invasion during carcinogenesis. The cadherin-catenin proteins, like Hsps, are proteins with the capacity to bind other proteins. Moreover, there are common molecular pathways for the Hsp response and for the cadherin-catenin protein system. b-catenin was immunoprecipitated (IP) from breast cancer biopsy samples and the resulting product was probed with different antibodies against Hsp family members. b-catenin interacted with Hsp27 and HSF1 (heat shock transcription factor 1), this is the first demonstration of these specific interactions, b–catenin did not form complexes with Hsp60, Hsp70, Hsp90, gp96 and CHOP. To confirm this finding, the 27 kDa immunoprecipitated band was excised and submitted to LC-ESI-MSMS, and in this study the band was identified as Hsp27. In addition, b-catenin interacted with P-cadherin and caveolin-1. In the co-localization studies, b-catenin was observed in the same tumor areas and in the same tumor cells that expressed Hsp27. This association was strong when b-catenin was expressed in the cytoplasm of the tumor cells, not when b-catenin was expressed at the cell membrane. In addition, b-catenin co-localized with HSF1. Finally, the prognostic significance of cadherin-catenin proteins was examined by immunohistochemistry in breast cancer patients (n=215, follow-up: >10 years). Statistical analyses were performed using the Prism computer program: Kaplan-Meier method, difference between curves evaluated with the log-rank test for censored survival or event observations, contingency tables analyzed by the Fisher´s exact test and Chi-square with Yates´ correction. We found that the DFS and OS were significantly shorter for patients with P-cadherin positive immunostaining and cytoplasmic b-catenin positive tumors. 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.