Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice

被引:14
作者
Liu, ML
Shibata, MA
Von Lintig, FC
Wang, WL
Cassenaer, S
Boss, GR
Green, JE [1 ]
机构
[1] NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA
[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
关键词
Ki-ras; mammary gland tumor; transgenic mice;
D O I
10.1038/sj.onc.1204280
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have previously demonstrated that amplification and overexpression of the Ki-ras gene is associated with mammary tumor progression in C3(1)/SV40Tag transgenic mice (Liu Et al,, 1998), To further evaluate the functional significance of the Ki-vas proto-oncogene in mammary cancer development, in vivo studies were conducted to examine the effect of Ki-vas gene dosage on tumor progression. The lack of one normal Ki-vas allele C3(1)/SV40Tag transgenic mice resulted in significantly delayed mammary intraepithelial neoplasia (MIN) formation as well as in a decreased number of mammary gland carcinomas, However, despite the retardation of tumor development by reduced Ki-ras gene dosage, overall survival was only modestly affected. This appears to be due to several factors including significant mammary tumor growth associated with Ki-ras gene amplification and over-expression that occurs during the advanced stage of oncogenesis in mice carrying either one or two normal Ki-ras alleles, The retardation of tumor progression due to the haploid loss of Ki-ras did not appear to be related to accelerated apoptosis, or a reduced rate of cell proliferation at the tumor stages examined. These data strongly suggest that the gene dosage of Ki-vas affects tumor promotion at an early stage of mammary tumor progression in this SV40 Tag-induced model of mammary oncogenesis.
引用
收藏
页码:2044 / 2049
页数:6
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