PSMD3 is a differentially expressed gene in human metastatic breast cancer, in the brain and in the lymph nodes.
Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that proteasome 26S subunit, non-ATPase 3, encoded by PSMD3, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. PSMD3 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of PSMD3 in primary tumors was significantly correlated with patient recurrence-free survival in patients with breast cancer. Modulation of PSMD3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer. The data suggest that changes in proteasome dynamics may occur during progression of human metastatic breast cancer.