ß-catenin interacts with heat shock protein Hsp27 and heat shock transcription factor 1 and it is a useful prognostic marker in breast cancer patients

GAGO FE; FANELLI MA; MONTT GUEVARA MM; DIBLASI AM; TELLO O; CUELLO CARRIÓN DF; CALLEGARI E; CIOCCA DR

Chicago, Estados Unidos

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

American Society of Clinical Oncology

We examined in breast cancer the possible interactions between heat shock proteins (Hsps) and the cadherin- catenin cell adhesion proteins, which have important roles in signaling pathways and tumor cell invasion. The cadherin-catenin proteins, like Hsps, have the capacity to bind other proteins. Moreover, there are common molecular pathways for the Hsp response and for the cadherin- catenin protein system. Methods: ß-catenin was immunoprecipitated from breast cancer biopsies and the resulting product was probed with antibodies against Hsp members. LC-ESI-MSMS analysis was performed. Immunohistochemistry was used on paraffin sections. Statistical analyses were performed (Prism computer program): Kaplan-Meier, 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. Results: ß- catenin interacted with Hsp27 and HSF1 (heat shock transcription factor 1), this is the first demonstration of these specific interactions, ß- catenin did not interact with Hsp60, Hsp70, Hsp90, gp96 and CHOP. To confirm this finding, the 27 kDa band was excised and submitted to LC- ESI-MSMS, the band was identified as Hsp27. In addition, ß-catenin interacted with P-cadherin and caveolin-1. In the co-localization studies, ß- catenin was observed in the same tumor areas and cells that expressed Hsp27. This association was strong when ß-catenin was expressed in the cytoplasm, not when ß-catenin was expressed at the cell membrane. In addition, ß-catenin co-localized with HSF1. Finally, the prognostic significance of cadherin-catenin proteins was examined in breast cancer patients (n=215, follow-up: >10 years). Conclusions: We found that cytoplasmic ß-catenin interacted with Hsp27 and HSF1, and that the survival (disease free and overall) was significantly shorter for patients with P-cadherin + and cytoplasmic ß-catenin + tumors. The interactions of ß-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.