The
ubiquitin (Ub)/
proteasome pathway facilitates the degradation of damaged
proteins and regulators of growth and stress response. The activation of this pathway in various
cancers and
malignancies has been described, and several genetic determinants of
breast cancer, including BRCA1 and BRCA2, are linked to protein degradation. To investigate the involvement of the Ub/
proteasome system in
breast cancer, we examined a collection of 25 patient-matched
breast cancer and normal adjacent tissues and detected activation of numerous components of the Ub/
proteasome pathway. The activity of the
proteasome, and levels of
proteasome subunits and various targeting factors, were increased in >90% of primary
breast cancer tissue specimens. In contrast, no activation was observed in benign solid
tumors, indicating that the response is specific to abnormal growth in neoplastic cells. Additionally, the accumulation of high levels of certain Ub-conjugating
enzymes (UbcH1, UbcH2, and UbcH5), was specific to
breast cancer, as no change in abundance was detected in primary
colon cancer tissue extracts. Surprisingly, the Ub/
proteasome system was not activated in a well-characterized cell culture-based
breast cancer model system. Collectively, these findings suggest that the analysis of primary
breast cancer tissue samples will be indispensable for the biochemical characterization of neoplastic growth and for the development of
therapeutics.