Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland

To investigate the role of beta -catenin in mammary gland development and n eoplasia, we expressed a stabilized, transcriptionally active form of beta -catenin lacking the NH2-terminal 89 amino acids (Delta N89 beta -catenin) under the control of the mouse mammary tumor virus long terminal repeat. Ou r results show that Delta N89 beta -catenin induces precocious loburoalveol ar development and differentiation in the mammary glands of both male and f emale mice. Virgin Delta N89 beta -catenin mammary glands resemble those fo und in wild-type (wt) pregnant mice and inappropriately express cyclin 191 mRNA. In contrast to wt mammary glands, which resume a virgin appearance af ter cessation of lactation, transgenic mammary glands involute to a midpreg nant status. All transgenic females develop multiple aggressive adenocarcin omas early in life. Surprisingly, the Delta N89 beta -catenin phenotype dif fers from those elicited by overexpression of Wnt genes in this gland. In p articular, Delta N89 beta -catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional do wnstream effecters or modulators.