Src tyrosine kinase is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.
Trastuzumab (Herceptin), a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1), is 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 fashion the most significant transcriptional changes associated with treatment with trastuzumab in patients with breast cancer. We identified the proto-oncogene and tyrosine kinase Src 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 Src messenger than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of Src in primary tumors of the breast, demonstrating that a proto-oncogene (5) and gene whose product is necessary to drive MMTV-induced tumorigenesis of the mammary gland in mice6 is transcriptionally induced in primary tumors of the breast, likely as a direct result of treatment with trastuzumab.