Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models Journal Article

   


Authors: Du, Z.; Podsypanina, K.; Huang, S.; McGrath, A.; Toneff, M. J.; Bogoslovskaia, E.; Zhang, X.; Moraes, R. C.; Fluck, M.; Allred, D. C.; Lewises, M. T.; Varmus, H. E.; Li, Y.
Article Title: Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models
Abstract: We have adapted the avian leukosis virus RCAS (replication-competent avian sarcoma-leukosis virus LTR splice acceptor)-mediated somatic gene transfer technique to introduce oncogenes into mammary cells in mice transgenic for the avian subgroup A receptor gene, tva, under control of the mouse mammary tumor virus (MMTV) promoter. Intraductal instillation of an RCAS vector carrying the polyoma middle T antigen (PyMT) gene (RCAS-PyMT) induced multiple, oligoclonal tumors within 3 weeks in infected mammary glands of MMTV-tva transgenic mice. The rapid appearance of these tumors from a relatively small pool of infected cells (estimated to be ≈2 × 103 cells per gland by infection with RCAS carrying a GFP gene; RCAS-GF0P) was accompanied by a high fraction of cells positive for Ki67, Cyclin D1, and c-Myc, implying strong proliferation competence. Furthermore, the tumors displayed greater cellular heterogeneity than did tumors arising in MMTV-PyMT mice, suggesting that RCAS-PyMT transforms a relatively immature cell type. Infection of mice transgenic for both MMTV-Wnt-1 and MMTV-tva with RCAS virus carrying an activated Neu oncogene dramatically enhanced tumor formation over what is observed in uninfected bitransgenic animals. We conclude that infection of mammary glands with retrovirus vectors is an efficient means to screen candidate oncogenes for their capacity to initiate or promote mammary carcinogenesis in the mouse. © 2006 by The National Academy of Sciences of the USA.
Keywords: controlled study; survival rate; unclassified drug; nonhuman; ki 67 antigen; cell proliferation; animal cell; mouse; animals; mice; animal tissue; breast cancer; animal experiment; animal model; in vitro study; avian leukosis oncovirus; gene transfer; transgenic mouse; animalia; avian leukosis virus; mus musculus; genetic vectors; mice, transgenic; cell heterogeneity; cell transformation, neoplastic; aves; myc protein; retrovirus vector; epithelial cells; disease models, animal; cyclin d1; oncogene c myc; proto-oncogene proteins c-myc; polyoma middle t antigen; antigens, polyomavirus transforming; erbb2; breast carcinogenesis; mammary glands, animal; mammary gland; mouse mammary tumor virus; wnt; oncogene neu; virus gene; oncogenic viruses; mouse mammary tumor oncovirus; virus middle t antigen; subgroup a; gfp gene; tumor virus a; rcas pymt; pymt gene; replication competent avian sarcoma leukoma virus ltr splice acceptor; somatic gene therapy; avian sarcoma viruses
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 103
Issue: 46
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2006-11-14
Start Page: 17396
End Page: 17401
Language: English
DOI: 10.1073/pnas.0608607103
PUBMED: 17090666
PROVIDER: scopus
PMCID: PMC1635021
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-33751244557&partnerID=40&md5=80378a95f6423b7dfd095924a7142fed
Notes: --- - "Cited By (since 1996): 28" - "Export Date: 4 June 2012" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Katrina Podsypanina
    15 Podsypanina
  2. Harold Varmus
    96 Varmus
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