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

CUELLO-CARRION D; JORGE SHORTREDE; ALVAREZ OLMEDO D; N. CAYADO-GUTIÉRREZ,; CASTRO G. N.; GAGO EF; CIOCCA L; FANELLI MA; CIOCCA D.R.

Congreso; VI International Congress on cell stress society international; 2013

Breast cancer cells show β-catenin/HER-2 interaction, both proteins cooperate inducing mammary tumors in transgenic mice. In addition, β-catenin interacts with HSP27. We reported a striking membrane β-catenin/HER-2 expression in transgenic mice (in contrast to human breast cancer where β-catenin frequently appears in the cytoplasm). We report here the clinical significance of β-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, β-catenin was expressed in the membrane only (HER-2 was absent). In hyperplastic lesions and in in situ carcinomas β-catenin appeared in the membrane and cytoplasm, and some cells lost its expression. HER-2 appeared in in situ carcinomas only. In invasive carcinomas β-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 β-catenin in the form of continuous membrane immunostaining, there was a strong association with good prognosis. To further explore the dynamics of β -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 β-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 β-catenin and HER-2 and represent a step towards more individualized diagnostic/treatment concepts in human breast cancer.