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Using mouse models to understand the...
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Backlund, Michael George.
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Using mouse models to understand the role of tumor suppressor genes in development and tumorigenesis.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Using mouse models to understand the role of tumor suppressor genes in development and tumorigenesis./
作者:
Backlund, Michael George.
面頁冊數:
243 p.
附註:
Director: Beverly H. Koller.
Contained By:
Dissertation Abstracts International64-03B.
標題:
Biology, Genetics. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3086487
Using mouse models to understand the role of tumor suppressor genes in development and tumorigenesis.
Backlund, Michael George.
Using mouse models to understand the role of tumor suppressor genes in development and tumorigenesis.
- 243 p.
Director: Beverly H. Koller.
Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2003.
Breast cancer is the most common cancer in women in the western world, with approximately one in ten women developing this disease. In breast cancer development, both genetic and environmental factors play a role, with inheritance of high penetrance susceptibility genes, <italic>BRCA1</italic> and <italic> BRCA2</italic>, accounting for approximately 5% of all cases. In order to understand the role of tumor suppressor genes in regulation of normal cell growth and in prevention of mammary tumor formation, I have taken a genetic approach, through the use of genetically engineered mice deficient in the expression of tumor suppressor genes <italic>Brca1</italic>, <italic>Trp53 </italic>, and <italic>Rb</italic>, to address specific questions concerning the pathophysiology of mammary carcinogenesis.Subjects--Topical Terms:
1017730
Biology, Genetics.
Using mouse models to understand the role of tumor suppressor genes in development and tumorigenesis.
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Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2003.
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Breast cancer is the most common cancer in women in the western world, with approximately one in ten women developing this disease. In breast cancer development, both genetic and environmental factors play a role, with inheritance of high penetrance susceptibility genes, <italic>BRCA1</italic> and <italic> BRCA2</italic>, accounting for approximately 5% of all cases. In order to understand the role of tumor suppressor genes in regulation of normal cell growth and in prevention of mammary tumor formation, I have taken a genetic approach, through the use of genetically engineered mice deficient in the expression of tumor suppressor genes <italic>Brca1</italic>, <italic>Trp53 </italic>, and <italic>Rb</italic>, to address specific questions concerning the pathophysiology of mammary carcinogenesis.
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In this dissertation I address whether mammary tumorigenesis in mice is influenced by the loss of individual or sets of tumor suppressor genes, in combination with specific sets of modifier alleles present on inbred mouse strains. Mice heterozygous for a <italic>Trp53</italic> mutation on an inbred BALB/c background are shown to be susceptible to mammary tumors, and both the tumor incidence and latency associated with these animals can be altered by hormonal stimulation, exposure to ionizing radiation, and introduction of a <italic>Brca1</italic> mutation.
520
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Furthermore, I show that similar interactions between tumor suppressor genes and modifier genes observed in normal cells also play an important role during the development of the embryo. Mice homozygous for a <italic>Brca1 </italic> mutation die <italic>in utero</italic>, and I show that the stage of development at which embryonic lethality occurs is altered not only by the severity of the introduced <italic>Brca1</italic> mutation, but by the genetic background in which the <italic>Brca1</italic> is bred. Finally, I show that heterozygosity for a mutant <italic>Trp53</italic> allele is sufficient and equal to complete loss p53 function to maintain growth and survival of <italic> Brca1−</italic>/− embryos, thus allowing a small number of <italic> Brca1</italic>−/−<italic>Trp53</italic>−/− and <italic> Brca1</italic>−/−<italic>Trp53</italic>+/− mice to survive beyond parturition. These findings demonstrate the important roles that tumor suppressors like <italic>Brca1</italic> and <italic>Trp53</italic> play in regulation of cell growth and the prevention of tumorigenesis.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3086487
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