Spi1 (PU.1) 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 transcription factor Spi1 (PU.1) 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 Spi1 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of Spi1 in primary tumors of the breast, demonstrating increased expression of a transcription factor whose transgenic expression in mice results in development of erythroleukemia and that guides fate choice to microglial lineages from that of hematopoietic cells (5, 6) as a direct transcriptional result of treatment with trastuzumab.