DIFFERENTIAL TRANSFORMATION OF MAMMARY EPITHELIAL-CELLS BY WNT GENES

The mouse Wnt family includes at least 10 genes that encode structural ly related secreted glycoproteins. Wnt-1 and Wnt-3 were originally ide ntified as oncogenes activated by the insertion of mouse mammary tumor virus in virus-induced mammary adenocarcinomas, although they are not expressed in the normal mammary gland. However, five other Wnt genes are differentially expressed during development of adult mammary tissu e, suggesting that they mag play distinct roles in various phases of m ammary gland growth and development. Induction of transformation by Wn t-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis. We h ave tested Wnt family members for the ability to induce transformation of cultured mammary cells. The results demonstrate that the Wnt gene family can be divided into three groups depending on their ability to induce morphological transformation and altered growth characteristics of the C57MG mammary epithelial cell line. Wnt-1, Wnt-3A, and Wnt-7A were highly transforming and induced colonies which formed and shed ba lls of cells, Wnt-2, Wnt-5B, and Wnt-7B also induced transformation bu t with a lower frequency and an apparent decrease in saturation densit y. In contrast, Wnt-6 and two other family members which are normally expressed in C57MG cells, Wnt-4 and Wnt-5A, failed to induce transform ation. These data demonstrate that the Wnt genes have distinct effects on cell growth and should not be regarded as functionally equivalent.