ITGβ1 (CD29) 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 cell adhesion molecule integrin β1 (5-9) 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 significantly higher levels of ITGβ1 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of ITGβ1 in primary tumors of the breast, suggesting that increased primary tumor expression of ITGβ1 in the primary tumors of patients with breast cancer, a molecule whose increased expression in human breast cancer is correlated with overall survival, metastasis and significantly decreased time from diagnosis to death (10, 11), is a direct transcriptional result of treatment with trastuzumab.