gms | German Medical Science

Plakoglobin = gamma-catenin is an important protein of cellular adhesion structures in epithelia. It is part of the desmosomal plaque as of the adherens junctions as well. Together, both structures account for more than 90% of total cell-cell adhesion. During the metastatic processthis adhesion has to be broken before tumor cells are able to disseminate. Since plakoglobin is part of both important adhesive structures it might be a central candidate for downregulation during dedifferentiation and malignant transformation. In a retrospective study we have determined the plakoglobin expression in breast carcinomas and correlated it with the clinical outcome of the patients. In addition, several human breast cancer cell lines were tested for plakoglobin expression and for invasiveness in Boyden chamber experiments.

Material and Methods: 86 specimens were tested for plakoglobin by means of immunohistochemistry and the expression scored separately for membrane, cytosol, and nucleus. Mean plakoglobin values were evaluated for the two groups of surviving and deceased tumor patients. The plakoglobin expression of 6 human breast cancer cell lines was determined by Western blotting and correlated with invasiveness in matrigel coated filter inserts (Boyden chambers).

Results: In a 15 years follow-up the ratio surviving/deceased was 2.2 for membrane, 1.6 for nucleus, 1.2 for cytosol, and 1.4 for overall staining. All patients with an intense staining of either membrane or nucleus are still alive, in contrast to about 40% survival for low membrane or low nuclear staining and 12% survival for low both. Similar results were obtained in vitro: the higher the expression of plakoglobin the lower the invasiveness of a cell line and vice versa.

Discussion: In conclusion, we found a close correlation of conserved plakoglobin expression in the tumor with survival over 15 years, in particular for membraneous and nuclear staining. In the nucleus plakoglobin might compete withthe homologous beta-catenin which acts as proliferative transcription factor in some oncogenic pathways. In cultured cancer cells we found a similarinverse correlationof plakoglobin expression with aggressiveness of the tumor cell.