DCC is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.
Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the deleted in colorectal cancer locus DCC (5, 6) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of DCC messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of DCC in primary tumors of the breast, demonstrating that a gene encoding for a netrin receptor, cellular machinery utilized for axon guidance in the central nervous system (5-9), is transcriptionally induced in primary tumors of the breast following treatment with trastuzumab.