We noted enhanced phosphorylated Akt and MAPK in a perivascular distribution in mammary tumors, with overexpression of both erbB2 and erbB3 (Fig. 6), suggesting that circulating HRG may enhance the physical and functional erbB2/erbB3 interactions in vivo, similar to what we observe in vitro. This evidence concerns the gene ERBB2 and breast cancer.