Differential Transformation of Mammary Epithelial Cells by <i>Wnt</i> Genes

TLDR

The mouse Wnt family comprises at least ten secreted glycoproteins, with Wnt‑1 and Wnt‑3 acting as oncogenes absent from normal mammary tissue, while five other Wnt genes are differentially expressed during adult mammary development, implying distinct roles in gland growth and suggesting that Wnt‑1/3‑induced transformation may disrupt normal regulatory events, though direct evidence is lacking. We tested Wnt family members for their ability to induce transformation in cultured mammary cells. The study classified Wnt genes into three groups by their transformation potency in C57MG cells: Wnt‑1, 3A, and 7A were highly transforming, Wnt‑2, 5B, and 7B induced transformation at lower frequency, whereas Wnt‑4, 5A, and 6 failed to transform, demonstrating distinct effects on mammary epithelial cell growth.

Abstract

The mouse Wnt family includes at least 10 genes that encode structurally related secreted glycoproteins. Wnt-1 and Wnt-3 were originally identified 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 tissue, suggesting that they may play distinct roles in various phases of mammary gland growth and development. Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis. We have 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 balls of cells. Wnt-2, Wnt-5B, and Wnt-7B also induced transformation but with a lower frequency and an apparent decrease in saturation density. In contrast, Wnt-6 and two other family members which are normally expressed in C57MG cells, Wnt-4 and Wnt-5A, failed to induce transformation. These data demonstrate that the Wnt genes have distinct effects on cell growth and should not be regarded as functionally equivalent.