Amplification of Ki-ras and elevation of MAP kinase activity during mammary tumor progression in C3(1)/SV40 Tag transgenic mice (original) (raw)

Oncogene volume 17, pages 2403–2411 (1998)Cite this article

Abstract

We have previously documented that transgenic mice expressing SV40 Tag regulated by the rat prostatic steroid-binding protein C3(1) 5′-flanking region display multistage mammary tumorigenesis. To delineate genetic changes associated with mammary tumor progression, comparative genomic hybridization (CGH) was performed. CGH revealed a consistent gain of the telomeric region of chromosome 6. This region contains the Ki-ras proto-oncogene. Analyses of genomic DNA by Southern blot demonstrated up to 40-fold amplification of the Ki-ras gene. Ki-ras amplification was detected in 12, 46 and 68% of tumors from 4, 5 and 6 month old mice, respectively, whereas no amplifications were found in any preneoplastic mammary tissues. Tumors bearing Ki-ras gene amplification exhibited high levels of Ki-ras RNA and protein. The over-expressed Ki-Ras protein in these tumors appeared functionally active as indicated by the elevated MAP kinase activity. These data demonstrate that while Ki-ras amplification might not be an early event, there is a strong association between Ki-ras amplification and over-expression and mammary tumor progression in this model. This study also shows that CGH is a powerful and useful technique for identifying chromosomal copy number changes during tumor progression, and that this model may provide a predictable in vivo system for studying gene amplification.

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Authors and Affiliations

  1. Division of Basic Science, Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Building 41/Room C619, Bethesda, 20892, Maryland, USA
    Min-Ling Liu, Masa-Aki Shibata, Cheryl L Jorcyk & Jeffrey E Green
  2. Department of Medicine, University of California, San Diego, California, USA
    Friederike C Von Lintig & Gerry R Boss
  3. National Human Genome Research Institute, NIH, Bethesda, Maryland, USA
    Marek Liyanage & Thomas Ried

Authors

  1. Min-Ling Liu
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  2. Friederike C Von Lintig
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  3. Marek Liyanage
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  4. Masa-Aki Shibata
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  5. Cheryl L Jorcyk
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  6. Thomas Ried
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  7. Gerry R Boss
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  8. Jeffrey E Green
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Liu, ML., Lintig, F., Liyanage, M. et al. Amplification of Ki-ras and elevation of MAP kinase activity during mammary tumor progression in C3(1)/SV40 Tag transgenic mice.Oncogene 17, 2403–2411 (1998). https://doi.org/10.1038/sj.onc.1202456

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