Amplification and proviral activation of several Wnt genes during progression and clonal variation of mouse mammary tumors.

TitleAmplification and proviral activation of several Wnt genes during progression and clonal variation of mouse mammary tumors.
Publication TypeJournal Article
Year of Publication1992
AuthorsRoelink H, Wagenaar E, Nusse R
JournalOncogene
Volume7
Pagination487–492
Date PublishedMar
ISSN0950-9232 (Print); 0950-9232 (Linking)
AbstractMammary tumors in the GR strain are caused by a dominant locus containing an endogenous mouse mammary tumor provirus. Expression of this locus results in high virus titers, inducing tumors that progress from a hormone-dependent to a hormone-independent tumor state. We previously studied the activation of the Wnt-1 and int-2 oncogenes in several series of transplanted GR tumors and found that hormone-dependent early passages are generally oligoclonal for proviral integration at these genes. We have now re-examined several such tumor series for activation of other Wnt genes. In one series, the transition to hormone-independent growth was marked by the loss of the oligoclonal genotype and outgrowth of a hormone-independent cell population, clonal for the activation of Wnt-3. We show two examples of series of transplanted tumors that in later hormone-independent passages contain an amplified and overexpressed Wnt-2 gene, a novel mode of activation of these genes.