P-cadherin and beta-catenin are useful prognostic factors in breast cancer and beta-catenin interacts with HSF-1 and Hsp-27

FANELLI M. A.; MONTT GUEVARA M. M.; GAGO F. E.; TELLO O.; VARGAS ROIG L. M.; CUELLO CARRIÓN F. D.; CIOCCA D. R.

Tomar, Portugal

Congreso; 2nd International Congress on Stress Responses in Biology and Medicine; 2005

Cell Stress Society International

We have evaluated by imrnunohistochemistry the prognostic significance of E-cadherin, P-cadherin and beta-catenin in breast cancer patients (n = 204, follow-up  =10 years). The overall survival and the disease free survival curves showed statistically significance for P-cadherin and beta-catenin. The localization of these proteins in the tumor cells was an important determinant for their prognostic significance. The high expression level of beta-catenin in the cytoplasm of several of the tumor samples conducted us to explore the potential interaction of beta-catenin with another proteins that have elevated expression levels and prognostic significance in breast cancer, the heat shock proteins (Hsps). Beta-catenin was immunoprecipitated (IP) with magnetic particles and the resulting product was probed with different antibodies against family members of the Hsps. Beta-catenin was interacting with Hsp27 and HSF1 (heat shock transcription factor 1), this is the first demonstration of these specific interactions, Beta-catenin did not form complexes with Hsp60, Hsp70, Hsp90, gp96 and CHOP. In addition, beta-catenin interacted with P-cadherin and caveolin-1. In the co-localization studies in the breast cancer biopsies, Beta-catenin was observed in the same tumor areas and in the same tumor cells that expressed Hsp27 and HSF1. These associations were statistically significant when Beta-catenin was expressed in the cytoplasm of the tumor cells, not when Beta-catenin was expressed at the cell membrane. The interactions of beta-catenin with HSF1 and Hsp27 may explain some of the molecular pathways that influence tumor cell survival and the clinical significance in the prognosis of breast cancer patients.