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. 2016 Nov 30;292(2):748–759. doi: 10.1074/jbc.M116.754960

FIGURE 2.

FIGURE 2.

RTKs mediating resistance are up-regulated in drug resistant tumors and cell lines as a result of HER2 inhibition. A and B, IGF1R, PDGFRb, and TYRO3 expression levels increase as a result of trastuzumab (TRA) treatment in drug-resistant breast cancer cells. rBT474 (A) or MDA-MB-361 (B) cells were cultured for 72 h in the presence of 1, 3, or 10 μm trastuzumab, after which cells were harvested and protein lysates were immunoblotted using the indicated antibodies. C–E, representative images and quantification of IGF1R, PDGFRb, and TYRO3 immunohistochemistry in resistant and sensitive tumors before and after neoadjuvant trastuzumab therapy. Samples were obtained from HER2-positive breast cancers by mammotome biopsy before therapy and from surgery after treatment. n = 19 sensitive tumors; 13 resistant tumors. Error bars, S.D.; ***, p < 0.01. See supplemental Table S3 for exact p values. F, frequency of RTK overexpression after HER2 inhibition based on immunohistochemistry analysis of unresponsive patient tumors. A green bar represents up-regulation of the indicated RTK in an individual tumor.