HER-2/neu and beta-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer a stressful situation

CUELLO CARRION F. D.; SHORTREDE J.; ALVAREZ OLMEDO D.; WUILLUOD R.; CAYADO-GUTIÉRREZ N.; CASTRO G. N.; GAGO F. E.; CIOCCA L.; FANELLI M. A.; CIOCCA D. R.

Sheffield

Congreso; VI International Congress on Stress Proteins in Biology and Medicine; 2013

Cell Stress Society International

Breast cancer cells show beta-catenin/HER-2 interaction, both proteins cooperate inducing mammary tumors in transgenic mice. In addition, beta-catenin interacts with HSP27. We reported a striking membrane beta-catenin/HER-2 expression in transgenic mice (in contrast to human breast cancer where beta-catenin frequently appears in the cytoplasm). We report here the clinical significance of beta-catenin/HER-2 association in our tumor bank by immunohistochemistry. These patients did not receive specific anti-HER-2 therapy. In ?normal? glands adjacent to tumors, beta-catenin was expressed in the membrane only (HER-2 was absent). In hyperplastic lesions and in in situ carcinomas beta-catenin appeared in the membrane and cytoplasm, and some cells lost its expression. HER-2 appeared in in situ carcinomas only. In invasive carcinomas beta-catenin appeared: a) at the cell membrane (completely surrounding the tumor cells), or b) as fragmented membrane immunostaining with or without cytoplasmic granules. Interestingly, in the HER-2 positive cancer patients, when the tumors expressed beta-catenin in the form of continuous membrane immunostaining, there was a strong association with good prognosis. To further explore the dynamics of beta-catenin/HER-2 interaction, we examined the behavior of these proteins when MCF-7 cells were exposed to a stressful situation (Cd administration). Cd induced a beta-catenin shift from the cell membrane to the cytoplasm, at Cd concentrations that affected long-term survival. HER-2 was also affected by Cd administration, the protein remained at the cell membrane but its expression increased significantly in the cytoplasm. These studies point to the links between beta-catenin and HER-2 and represent a step towards more individualized diagnostic/treatment concepts in human breast cancer.