SYK, CSK and FYN are differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.
The mechanism of action underlying trastuzumab (Herceptin) function is ascribed to binding of the Fab region of trastuzumab to the extracellular domain of the human epidermal growth factor receptor (HER2) (1). The transcriptional responses that follow signals transduced after trastuzumab binding of HER2 are less well understood. Protein tyrosine kinases are one major class of cellular components utilized in the transduction of signals from the cell surface to the nucleus. We mined published microarray and multiplexed gene expression data (2-5) to understand in an unbiased fashion genes most differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab. We observed significantly increased and differential expression of multiple protein tyrosine kinases in the primary tumors of patients with breast cancer, including SYK, CSK and FYN. These data document previously undescribed up-regulation of protein tyrosine kinases following treatment with trastuzumab in patients with breast cancer.