Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice.
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-ras proto-oncogene in mammary cancer development, in vivo studies were conducted to examine the effect of Ki-ras gene dosage on tumor progression. The lack of one normal Ki-ras 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-ras affects tumor promotion at an early stage of mammary tumor progression in this SV40 Tag-induced model of mammary oncogenesis.
Liu
M L
ML
Laboratory of Cell Regulation and Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institute of Health, Bethesda, Maryland, MD 20892, USA.
Shibata
M A
MA
Von Lintig
F C
FC
Wang
W
W
Cassenaer
S
S
Boss
G R
GR
Green
J E
JE
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D018450:Disease Progression; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006238:Haploidy; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
D000952:Antigens, Polyomavirus Transforming