Cooperative Effects of Tumor Suppressor Genes and Oncogenes on the Dynamic Process of Tumorigenesis

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dc.contributor.advisor Philip Sannes, Committee Member en_US
dc.contributor.advisor David Malarkey, Committee Member en_US
dc.contributor.advisor Robert Sills, Committee Co-Chair en_US
dc.contributor.advisor John M. Cullen, Committee Chair en_US
dc.contributor.author Houle, Christopher David en_US
dc.date.accessioned 2010-04-02T18:32:14Z
dc.date.available 2010-04-02T18:32:14Z
dc.date.issued 2005-07-18 en_US
dc.identifier.other etd-07062005-172704 en_US
dc.identifier.uri http://www.lib.ncsu.edu/resolver/1840.16/3567
dc.description.abstract The overall hypothesis of this dissertation was that certain mutations or altered proteins would have a greater tumorigenic effect if acting cooperatively rather than independently. Three studies were conducted in support of this hypothesis. The first study evaluated cooperative interactions between Brca2 and p53. The effects of mutation of these genes on cell proliferation and apoptosis were evaluated in the developing mouse mammary gland with and without exposure to irradiation. The hypothesis was that combined mutation of both genes would produce a more deleterious response than mutation of either gene alone. Results demonstrated that individual mutation of Brca2 or p53 could alter apoptosis and/or cell proliferation but had little effect on the growth index (apoptosis:proliferation ratio). Combined mutation of both genes did alter the growth index, but only in response to irradiation. The second study evaluated spontaneous, ethylene oxide-, and benzene-induced mouse mammary tumors for p53 and H-ras mutations. The hypothesis was that both p53 and H-ras mutations would commonly occur together in the chemically induced tumors but not in spontaneous tumors. Results revealed that p53 and H-ras mutations were common events in both chemically induced and spontaneous mammary tumors. Overall, the results revealed that cooperative interaction between these genes is important in the genesis of mouse mammary tumors in general. The third study evaluated the protein expression of four cell adhesion molecules (KAI1, CD9, E-cadherin, and N-cadherin) in ovarian epithelial carcinomas and metastases. The hypothesis was that more than one but not all of these adhesion molecules would be downregulated as tumors progressed towards a metastatic phenotype. Results revealed the remarkable complexity of adhesion molecule modulation during metastasis and suggested that cooperative interaction is an important event in the metastatic process. In conclusion, this dissertation evaluated cooperative interactions between several different classes of cancer-related genes and proteins and provided support for the hypothesis that particular mutations or altered proteins would have a greater tumorigenic effect if acting cooperatively rather than independently. en_US
dc.rights I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. en_US
dc.subject ethylene oxide en_US
dc.subject benzene en_US
dc.subject mammary gland en_US
dc.subject CD9 en_US
dc.subject E-cadherin en_US
dc.subject N-cadherin en_US
dc.subject H-ras en_US
dc.subject radiation en_US
dc.subject oncogenes en_US
dc.subject tumorigenesis en_US
dc.subject mammary carcinomas en_US
dc.subject ovarian carcinomas en_US
dc.subject tumor suppressor genes en_US
dc.subject KAI1 en_US
dc.subject p53 en_US
dc.subject Brca2 en_US
dc.title Cooperative Effects of Tumor Suppressor Genes and Oncogenes on the Dynamic Process of Tumorigenesis en_US
dc.degree.name PhD en_US
dc.degree.level dissertation en_US
dc.degree.discipline Comparative Biomedical Sciences en_US


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