Transportin 3 (Importin 12) is a differentially expressed gene in both lymph node and brain metastases in human breast cancer.
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 nuclear import receptor transportin 3, also known as transportin-SR2 or importin 12, encoded by TNPO3, was among the genes whose expression was most quantitatively different in the brain metastases of patients with metastatic breast cancer. TNPO3 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of TNPO3 in primary tumors was significantly correlated with patient recurrence-free survival in patients with breast cancer. Modulation of TNPO3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain. These data are one piece of evidence suggesting a common ancestor or tumor clone for brain and lymph node metastases that originate from the primary tumor, alluding to patterns in developmental origin and migratory pathways through the lymph node in human brain metastatic breast cancer.