No abstract

Pathologic examination and considering known clinical history may be helpful to differentiate the primary breast cancer and metastatic cancer. Metastasis to the breast from an extramammary neoplasm usually indicates disseminated metastatic disease and a poor prognosis. An accurate diagnosis of breast metastases, differentiating primary from metastatic breast carcinoma, is important for proper management.

b-arrestin 1 and 2 (also known as arrestin 2 and 3) are homologous adaptor proteins that regulate seven-transmembrane receptor trafficking and signalling. Other proteins with predicted 'arrestin-like' structural domains but lacking sequence homology have been indicated to function like b-arrestin in receptor regulation. We demonstrate that b-arrestin2 is the primary adaptor that rapidly binds agonist-activated b 2 adrenergic receptors (b 2 ARs) and promotes clathrin-dependent internalization, E3 ligase Nedd4 recruitment and ubiquitin-dependent lysosomal degradation of the receptor. The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized b 2 AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of b-arrestin2. Rather, the role of ARRDC proteins is to traffic Nedd4-b 2 AR complexes to a subpopulation of early endosomes.