The slit guidance ligand 1, SLIT1, 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 significant transcriptional changes associated with trastuzumab treatment. We identified the slit guidance ligand 1, encoded by SLIT1, 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 SLIT1 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of SLIT1 in primary tumors of the breast, demonstrating increased expression of a ligand involved in guidance of axon migration in the central nervous system (5-9) as a direct transcriptional consequence of treatment with trastuzumab.