As an example of the complexity underlying IGFBP-3 activity, the IGFBP-3-associated enhancement of EGFR signalling has been demonstrated to be dependent on the type of matrix protein present, such that breast cancer cells cultured on laminin in the presence of EGF show reduced growth in response to IGFBP-3 whereas, when cultured on fibronectin, their growth is stimulated by IGFBP-3 [49]. This evidence concerns the gene EGFR and breast carcinoma.