Lentivirus-mediated oncogene introduction into mammary cells in vivo induces tumors Journal Article
| Authors: | Siwko, S. K.; Bu, W.; Gutierrez, C.; Lewis, B.; Jechlinger, M.; Schaffhausen, B.; Li, Y. |
| Article Title: | Lentivirus-mediated oncogene introduction into mammary cells in vivo induces tumors |
| Abstract: | We recently reported the introduction of oncogene-expressing avian retroviruses into somatic mammary cells in ice susceptible to infection by transgenic expression of tva, encoding the receptor for subgroup A avian leukosis-sarcoma virus (ALSV). Because ALSV-based vectors poorly infect nondividing cells, they are inadequate for studying carcinogenesis initiated from nonproliferative cells (e.g., stem cells). Lentivirus pseudotyped with the envelope protein of ALSV infects nondividing TVA-producing cells in culture but has not previously been tested for introducing genes in vivo. Here, we demonstrate that these vectors infected mammary cells in vivo when injected into the mammary ductal lumen of mice expressing tva under the control of the keratin 19 promoter. Furthermore, intraductal injection of this lentiviral vector carrying the polyoma middle T antigen gene induced atypical ductal hyperplasia and ductal carcinoma in situ-like premalignant lesions in 30 days and palpable invasive tumors at a median latency of 3.3 months. Induced tumors were a mixed epithelial/myoepithelial histologic diagnosis, occasionally displayed squamous metaplasia, and were estrogen receptor-negative. This work demonstrates the first use of a lentiviral vector to introduce oncogenes for modeling cancer in mice, and this vector system may be especially suitable for introducing genetic alterations into quiescent cells in vivo. Copyright © 2008 Neoplasia Press, Inc. All rights reserved. |
| Keywords: | promoter region; nonhuman; animal cell; mouse; animals; mice; cells, cultured; breast neoplasms; transgenic mouse; viral gene delivery system; genetic vectors; mice, transgenic; oncogenes; cancer invasion; gene expression regulation; cancer genetics; oncogene; breast carcinoma; carcinoma in situ; lentivirus; lentivirus vector; transgene; epithelium cell; gene control; polyoma virus; myoepithelium cell; genetic disorder; estrogen receptor; antigens, polyomavirus transforming; breast carcinogenesis; mammary glands, animal; receptor gene; nih 3t3 cells; breast cell; hiv; cell transformation, viral; breast hyperplasia; myoepithelioma; virus gene; latent period; precancer; breast duct; promoter regions (genetics); virus middle t antigen; avian protein; squamous cell metaplasia; alpharetrovirus; keratin-9 |
| Journal Title: | NeoPlasia |
| Volume: | 10 |
| Issue: | 7 |
| ISSN: | 1522-8002 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2008-07-01 |
| Start Page: | 653 |
| End Page: | 662 |
| Language: | English |
| DOI: | 10.1593/neo.08266 |
| PUBMED: | 18592025 |
| PROVIDER: | scopus |
| PMCID: | PMC2435599 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "CODEN: NEOPF" - "Source: Scopus" |
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