Using the ITAM-containing envelope protein of MMTV Env and a chimeric B-cell receptor protein, many researchers have made several key observations (Katz et al, 2005; Grande et al, 2006; Ross et al, 2006): (1) ITAM-containing protein expression can transform immortalised normal MECs in three-dimensional (3D) culture; (2) ITAM-induced transformation is dependent on its tyrosine phosphorylation and is associated with downstream Src and Syk kinase activation and (3) mutation of the ITAM tyrosines reduces tumour induction markedly by MMTV in vivo and influences its genomic integration. This evidence concerns the gene ERVW-1 and neoplasm.