已为您找到该学者8条结果 成果回收站
【期刊论文】High metastatic potential in mice inheriting a targeted p53 missense mutation
刘耕, Geng Liu*, Timothy J. McDonnell†, Roberto Montes de Oca Luna*‡, Mini Kapoor*, Betsy Mims*, Adel K. El-Naggar§, and Guillermina Lozano*¶
4174-4179, PNAS, April 11, 2000, vol. 97, no.8,-0001,():
-1年11月30日
To understand the relevance of p53 missense mutations in vivo, we generated a mouse containing an arg-to-his substitution at p53 amino acid 172, which corresponds to the R175H hot-spot mutation in human tumors by homologous recombination. Inadvertently, this mouse contains the additional deletion of a G nucleotide at a splice junction that attenuates levels of mutant p53 to near wild-type levels. Mice heterozygous for the mutant allele differed from p53___ mice in tumor spectrum, with a significant increase in the number of carcinomas and a slight decrease in the number of lymphomas. More importantly, the osteosarcomas and carcinomas that developed in these mutant mice frequently metastasized (69% and 40%, respectively). In contrast, metastasis is rare in osteosarcomas of p53___ mice. Loss of heterozygosity studies of tumors indicated loss of heterozygosity in only 1 of 11 tumors. These data indicate clear differences between a p53 missense mutation and a null allele in tumorigenesis in vivo and suggest that the p53R172H_g mutant represents a gain-of-function allele.
-
64浏览
-
0点赞
-
0收藏
-
0分享
-
31下载
-
0
-
引用
【期刊论文】Mouse models dissect the role of p53 in cancer anddevelopment
刘耕, Guillermina LozanoU and Geng Liu
seminars in CANCER BIOLOGY, Vol 8, 1998: pp. 337-344,-0001,():
-1年11月30日
Mice lacking one or two copies of the p53 gene haveprovided invaluable insight into the process of tumorigenesis.The importance of apoptosis in suppression of tumorigenesisin vivo became evident from analysis of these mice.Moreover, the timing and kinds of tumors that develop inthese mice are altered by the presence of additional inheritedmutations, by strain differences, and by food intake. Developmentalabnormalities are also visible in mice with loss ofp53 and with overexpression of p53 suggesting that p53levels are critical for normal cellular processes. While mice donot necessarily recapitulate all the tumor types found ininherited cancers, they offer the unique opportunity to decipherthe critical pathways in tumorigenesis. These findingscan then be applied to humans.
tumor modelsr/, p53 rnull mice/, genetic interactionsr/, development
-
42浏览
-
0点赞
-
0收藏
-
0分享
-
52下载
-
0
-
引用
【期刊论文】Mutation of Phosphoserine 389 Affects p53 Function in Vivo*
刘耕, Mingming Hao‡, Andrew M. Lowy§, Mini Kapoor, Abdul Deffie¶, Geng Liu, andGuillermina Lozanoi
THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 271, No.46, Issue of November 15, pp. 29380-29385, 1996,-0001,():
-1年11月30日
To study the importance of phosphorylation for p53transactivation function, we generated mutations ateach of its known phosphorylated serine amino acids.Mutations of murine p53 serine residues individually toeither alanine or glutamic acid at positions 7, 9, 12, 18,37, 312, and 389 resulted in equivalent levels of transcriptionalactivation in standard transient transfectionexperiments. However, when p53 transcriptional activitywas measured in cells that attain G1 arrest uponcontact inhibition, wild-type p53 was inactive, and onlyalteration at serine 389 to glutamic acid resulted in afunctional p53 protein. This Ser 3 Glu mutant also hasan increased ability to bind DNA. Elimination of thephosphorylation site by substitution of an alanineamino acid resulted in loss of transcriptional activity.We also demonstrated that specific phosphorylation ofp53 at serine 389 is induced by cyclin E overexpressionin high-density cells. Our data establish for the first timethat phosphorylation of p53 at serine 389 is important inactivating its function in vivo.
-
26浏览
-
0点赞
-
0收藏
-
0分享
-
36下载
-
0
-
引用