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The genetic and biochemical analysis...
~
Freeman, Daniel Joseph.
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The genetic and biochemical analysis of Pten.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
The genetic and biochemical analysis of Pten./
作者:
Freeman, Daniel Joseph.
面頁冊數:
133 p.
附註:
Source: Dissertation Abstracts International, Volume: 64-01, Section: B, page: 0051.
Contained By:
Dissertation Abstracts International64-01B.
標題:
Biology, Genetics. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3076633
ISBN:
0493970657
The genetic and biochemical analysis of Pten.
Freeman, Daniel Joseph.
The genetic and biochemical analysis of Pten.
- 133 p.
Source: Dissertation Abstracts International, Volume: 64-01, Section: B, page: 0051.
Thesis (Ph.D.)--University of California, Los Angeles, 2003.
Tumor suppressor genes are an integral part of our anti-cancer defense. When these genes become inactive, tumors often develop. While the generally accepted model is that one allele is defective upon inheritance or mutation, then the remaining allele is somatically lost by loss of heterozygosity (LOH), a mechanism by which a large portion of the chromosome on which the normal allele resides is lost. Cells that are haploinsufficient (only have one functional copy of the gene) for a tumor suppressor gene, can also show loss of function after only one of the two alleles is altered. Recently, a novel tumor suppressor gene, PTEN (phosphatase and tensin homolog deleted on chromosome 10), was cloned and found to mutated in three rare, autosomal dominant disorders and many sporadic cancers. PTEN is the first tumor suppressor gene characterized to be a phosphatase. Biochemically, PTEN has dual specific phosphatase activity as well as lipid phosphatase activity, PIP3 being its primary target. The work presented here focuses on trying to understand the tumor suppressor functions of PTEN using murine genetic models. First, to determine if differences in PTEN mutations or genetic background/modifier genes are more important in determining the phenoypes seen in the genetic disorders, we report the consequences of the complete inactivation of Pten on both the 129/c57 and the 129/Balb/c genetic backgrounds. It is clear from this study that the genetic background is an essential determinant of the onset and spectrum of tumor progression. Second, again using a genetic model, we show that PTEN can control p53's protein level and more importantly p53's transcriptional activity, which in a compound heterozygous setting (Pten +/-;p53+/-) leads to the early onset of tumors, suggesting not only a role for PTEN in the nucleus, but also a mechanism by which one gene can control 'two hits' towards tumor progression. Third, using a genetic model, we use a naturally occurring mutation, which has been shown in vitro to loose its lipid phosphatase activity but retain its protein phosphatase activity, to show that PTEN may control pathways that are essential for learning and memory via its protein phosphatase activity.
ISBN: 0493970657Subjects--Topical Terms:
1017730
Biology, Genetics.
The genetic and biochemical analysis of Pten.
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Tumor suppressor genes are an integral part of our anti-cancer defense. When these genes become inactive, tumors often develop. While the generally accepted model is that one allele is defective upon inheritance or mutation, then the remaining allele is somatically lost by loss of heterozygosity (LOH), a mechanism by which a large portion of the chromosome on which the normal allele resides is lost. Cells that are haploinsufficient (only have one functional copy of the gene) for a tumor suppressor gene, can also show loss of function after only one of the two alleles is altered. Recently, a novel tumor suppressor gene, PTEN (phosphatase and tensin homolog deleted on chromosome 10), was cloned and found to mutated in three rare, autosomal dominant disorders and many sporadic cancers. PTEN is the first tumor suppressor gene characterized to be a phosphatase. Biochemically, PTEN has dual specific phosphatase activity as well as lipid phosphatase activity, PIP3 being its primary target. The work presented here focuses on trying to understand the tumor suppressor functions of PTEN using murine genetic models. First, to determine if differences in PTEN mutations or genetic background/modifier genes are more important in determining the phenoypes seen in the genetic disorders, we report the consequences of the complete inactivation of Pten on both the 129/c57 and the 129/Balb/c genetic backgrounds. It is clear from this study that the genetic background is an essential determinant of the onset and spectrum of tumor progression. Second, again using a genetic model, we show that PTEN can control p53's protein level and more importantly p53's transcriptional activity, which in a compound heterozygous setting (Pten +/-;p53+/-) leads to the early onset of tumors, suggesting not only a role for PTEN in the nucleus, but also a mechanism by which one gene can control 'two hits' towards tumor progression. Third, using a genetic model, we use a naturally occurring mutation, which has been shown in vitro to loose its lipid phosphatase activity but retain its protein phosphatase activity, to show that PTEN may control pathways that are essential for learning and memory via its protein phosphatase activity.
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