Reference SummaryLiu ML, Oncogene 1998 Nov 5;17(18):2403-11

Title

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

Authors

Liu ML; Von Lintig FC; Liyanage M; Shibata MA; Jorcyk CL; Ried T; Boss GR; Green JE

Journal

Oncogene

Volume

17

Issue

18

Year

1998

Pages

2403-11

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 tumori-genesis. 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.

Links

J:50935 – Mouse Genome Informatics
9811472 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(C3-1-TAg)cJeg Mammary gland adenocarcinoma Mammary gland

100

FVB/N-Tg(C3-1-TAg)cJeg Mammary gland hyperplasia Mammary gland

observed

FVB/N-Tg(C3-1-TAg)cJeg Mammary gland hyperplasia - nodular Mammary gland

observed