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. 1990 Jun;87(12):4519–4523. doi: 10.1073/pnas.87.12.4519

Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain.

H Roelink 1, E Wagenaar 1, S Lopes da Silva 1, R Nusse 1
PMCID: PMC54147  PMID: 2162045

Abstract

We have isolated a common insertion site, Wnt-3, for proviruses of the mouse mammary tumor virus (MMTV). Of mammary tumors induced by the GR variant of MMTV, 5% contains a provirus at Wnt-3, which is located on mouse chromosome 11. The gene is transcribed into a 3.8-kilobase (kb) mRNA in tumors with nearby proviral insertions but not in tumors with proviruses at other loci or in most adult tissues. Normal expression of Wnt-3 is detected in mouse embryos (with a peak around day 12 of gestation) and at low levels in adult brain. The transcriptional unit of the Wnt-3 gene spans approximately 55 kb, with a first intron of 36 kb. The deduced amino acid sequence of the Wnt-3 protein is 47% identical to the int-1/Wnt-1 gene product.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Buchberg A. M., Brownell E., Nagata S., Jenkins N. A., Copeland N. G. A comprehensive genetic map of murine chromosome 11 reveals extensive linkage conservation between mouse and human. Genetics. 1989 May;122(1):153–161. doi: 10.1093/genetics/122.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dickson C., Peters G. Potential oncogene product related to growth factors. 1987 Apr 30-May 6Nature. 326(6116):833–833. doi: 10.1038/326833a0. [DOI] [PubMed] [Google Scholar]
  3. Dickson C., Smith R., Brookes S., Peters G. Tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2. Cell. 1984 Jun;37(2):529–536. doi: 10.1016/0092-8674(84)90383-0. [DOI] [PubMed] [Google Scholar]
  4. Fung Y. K., Shackleford G. M., Brown A. M., Sanders G. S., Varmus H. E. Nucleotide sequence and expression in vitro of cDNA derived from mRNA of int-1, a provirally activated mouse mammary oncogene. Mol Cell Biol. 1985 Dec;5(12):3337–3344. doi: 10.1128/mcb.5.12.3337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gallahan D., Callahan R. Mammary tumorigenesis in feral mice: identification of a new int locus in mouse mammary tumor virus (Czech II)-induced mammary tumors. J Virol. 1987 Jan;61(1):66–74. doi: 10.1128/jvi.61.1.66-74.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  7. Hilkens J., van der Zeijst B., Buijs F., Kroezen V., Bleumink N., Hilgers J. Identification of a cellular receptor for mouse mammary tumor virus and mapping of its gene to chromosome 16. J Virol. 1983 Jan;45(1):140–147. doi: 10.1128/jvi.45.1.140-147.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jones-Villeneuve E. M., McBurney M. W., Rogers K. A., Kalnins V. I. Retinoic acid induces embryonal carcinoma cells to differentiate into neurons and glial cells. J Cell Biol. 1982 Aug;94(2):253–262. doi: 10.1083/jcb.94.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McMahon J. A., McMahon A. P. Nucleotide sequence, chromosomal localization and developmental expression of the mouse int-1-related gene. Development. 1989 Nov;107(3):643–650. doi: 10.1242/dev.107.3.643. [DOI] [PubMed] [Google Scholar]
  10. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mester J., Wagenaar E., Sluyser M., Nusse R. Activation of int-1 and int-2 mammary oncogenes in hormone-dependent and -independent mammary tumors of GR mice. J Virol. 1987 Apr;61(4):1073–1078. doi: 10.1128/jvi.61.4.1073-1078.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nusse R. The activation of cellular oncogenes by proviral insertion in murine mammary cancer. Cancer Treat Res. 1988;40:283–306. doi: 10.1007/978-1-4613-1733-3_14. [DOI] [PubMed] [Google Scholar]
  14. Nusse R. The int genes in mammary tumorigenesis and in normal development. Trends Genet. 1988 Oct;4(10):291–295. doi: 10.1016/0168-9525(88)90172-2. [DOI] [PubMed] [Google Scholar]
  15. Nusse R., van Ooyen A., Cox D., Fung Y. K., Varmus H. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature. 1984 Jan 12;307(5947):131–136. doi: 10.1038/307131a0. [DOI] [PubMed] [Google Scholar]
  16. Papkoff J. Inducible overexpression and secretion of int-1 protein. Mol Cell Biol. 1989 Aug;9(8):3377–3384. doi: 10.1128/mcb.9.8.3377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Peters G., Lee A. E., Dickson C. Concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus. Nature. 1986 Apr 17;320(6063):628–631. doi: 10.1038/320628a0. [DOI] [PubMed] [Google Scholar]
  18. Rijsewijk F., Schuermann M., Wagenaar E., Parren P., Weigel D., Nusse R. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell. 1987 Aug 14;50(4):649–657. doi: 10.1016/0092-8674(87)90038-9. [DOI] [PubMed] [Google Scholar]
  19. Robert B., Barton P., Minty A., Daubas P., Weydert A., Bonhomme F., Catalan J., Chazottes D., Guénet J. L., Buckingham M. Investigation of genetic linkage between myosin and actin genes using an interspecific mouse back-cross. Nature. 1985 Mar 14;314(6007):181–183. doi: 10.1038/314181a0. [DOI] [PubMed] [Google Scholar]
  20. Scharf S. J., Horn G. T., Erlich H. A. Direct cloning and sequence analysis of enzymatically amplified genomic sequences. Science. 1986 Sep 5;233(4768):1076–1078. doi: 10.1126/science.3461561. [DOI] [PubMed] [Google Scholar]
  21. Schuuring E., van Deemter L., Roelink H., Nusse R. Transient expression of the proto-oncogene int-1 during differentiation of P19 embryonal carcinoma cells. Mol Cell Biol. 1989 Mar;9(3):1357–1361. doi: 10.1128/mcb.9.3.1357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Todd J. A., Bell J. I., McDevitt H. O. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15;329(6140):599–604. doi: 10.1038/329599a0. [DOI] [PubMed] [Google Scholar]
  23. Wainwright B. J., Scambler P. J., Stanier P., Watson E. K., Bell G., Wicking C., Estivill X., Courtney M., Boue A., Pedersen P. S. Isolation of a human gene with protein sequence similarity to human and murine int-1 and the Drosophila segment polarity mutant wingless. EMBO J. 1988 Jun;7(6):1743–1748. doi: 10.1002/j.1460-2075.1988.tb03003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wilkinson D. G., Bailes J. A., McMahon A. P. Expression of the proto-oncogene int-1 is restricted to specific neural cells in the developing mouse embryo. Cell. 1987 Jul 3;50(1):79–88. doi: 10.1016/0092-8674(87)90664-7. [DOI] [PubMed] [Google Scholar]
  25. van Ooyen A., Nusse R. Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding domain intact. Cell. 1984 Nov;39(1):233–240. doi: 10.1016/0092-8674(84)90209-5. [DOI] [PubMed] [Google Scholar]
  26. van den Heuvel M., Nusse R., Johnston P., Lawrence P. A. Distribution of the wingless gene product in Drosophila embryos: a protein involved in cell-cell communication. Cell. 1989 Nov 17;59(4):739–749. doi: 10.1016/0092-8674(89)90020-2. [DOI] [PubMed] [Google Scholar]

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