The MUC1 Cytoplasmic Tail and Tandem Repeat Domains Contribute to Mammary Oncogenesis in FVB Mice

BACKGROUND: Though the importance of the transmembrane mucin MUC1 in mammary oncogenesis has long been recognized, the relative contributions of the cytoplasmic tail and tandem repeat domains are poorly understood. METHODS: To address this, mouse models of mammary carcinogenesis were created expressing full-length, cytoplasmic tail-deleted, or tandem repeat-deleted MUC1 constructs. RESULTS: Overexpression of full-length MUC1 resulted in tumor formation in young mice (≤12 months); however, loss of either the cytoplasmic tail or the tandem repeat domain abrogated this oncogenic capacity. Aged mice in all strains developed late-onset mammary tumors similar to those previously described for the FVB background. CONCLUSIONS: This study is the first spontaneous cancer model to address the relative importance of the cytoplasmic tail and tandem repeat domains to MUC1-driven mammary oncogenesis, and suggests that both of these domains are essential for tumor formation.