Amplification and proviral activation of several Wnt genes during progression and clonal variation of mouse mammary tumors.
Mammary 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.
Roelink
H
H
Howard Hughes Medical Institute, Beckman Center, Stanford University, California 94305.
Wagenaar
E
E
Nusse
R
R
D000818:Animals; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000235:genetics; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D005810:Multigene Family; D009857:Oncogenes; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D051153:Wnt Proteins; D051154:Wnt2 Protein; D060508:Wnt3 Protein
D004273:DNA, Neoplasm; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051153:Wnt Proteins; D051154:Wnt2 Protein; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse