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. Author manuscript; available in PMC: 2014 Jan 2.
Published in final edited form as: Nat Med. 2011 Mar 13;17(4):10.1038/nm.2309. doi: 10.1038/nm.2309

Figure 3.

Figure 3

SRC is a key modulator of trastuzumab response. (a) Immunoblots comparing SRC phosphorylation status in the indicated cells expressing a constitutively active SRC mutant (Y527F) or a kinase-dead SRC mutant (K295R). (b) MTS assay assessing trastuzumab sensitivity of cells transfected with SRC Y527F or SRC K295R mutant. Cells were treated as in Figure 1a. Error bars, s.e.m. (c) 3D tumor spheroid assay comparing response to trastuzumab treatment of BT474.GFP and BT474.SRC Y527F. 3D tumor spheroid assay was carried out as described in Online Methods. Scale bar, 100 µm. (d) Top, representative BT474 orthotopic xenograft tumors. Scale bar, 1 cm. Bottom, volume of mammary fat pad xenograft tumors derived from either GFP-labeled BT474 parental (GFP) or SRC Y527F–expressing cells upon treatment with IgG or Ttzm. Tumor volume at various times of treatment is percentage of original tumor size at day zero of treatment. Error bars, s.e.m. Ttzm-treated GFP group versus SRC Y527F group (ANOVA, P < 0.001, two-sided). (e) Correlation between clinical response rate and amount of tumor phospho-SRC-Y416 (pSRC) in patients who received first-line trastuzumab-based therapy. Complete response (CR), partial response (PR) and stable disease (SD) were grouped together and compared with SD. Patient response was compared by Fisher’s exact test (P = 0.011, two-sided). (f) Low versus high tumor phospho-SRC-Y416 abundance and overall survival of patients who received first-line trastuzumab-based therapy. Difference of overall survival was analyzed by Kaplan-Meier survival model with log-rank test (P = 0.044, two-sided).