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Organ development and tumorigenesis: a molecular link

Bonner, Allison E
http://rave.ohiolink.edu/etdc/view?acc_num=osu1073936508

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Medical Microbiology and Immunology.
The work presented in this dissertation aims to characterize molecular pathways involved in murine lung development, murine lung cancer development, and embryonic cancer development, in order to better understand the complex processes involved in the development and progression of lung cancer. Oligonucleotide microarray-based gene expression analysis was conducted across various stages of murine lung development to identify regulatory pathways at key developmental time points. Using Affymetrix U74Av2 Murine GeneChip® microarrays, 1,346 genes and ESTs were identified as having a significant change in expression. We also performed microarray analysis on a murine model of lung carcinogenesis, again using Affymetrix U74A GeneChips®. Epithelial lung cancers were induced in mice using NNK, a common carcinogen found in tobacco smoke, and gene expression analysis was performed on various stages of lung tumors. This analysis yielded 20 effectors involved in lung tumorigenesis and 50 effectors specific for tumor progression. We then compared the murine lung tumor results to the lung development study. This identified 24 developmentally regulated genes whose aberrant expression could contribute to tumor phenotype. To assess the relevance of murine lung cancer models in the study of human adenocarcinoma formation, we compared our murine lung tumor data to a study examining gene expression in human lung tumor samples and identified 39 genes with similar expression changes in human and murine lung tumors. This work links murine lung tumorogenesis to murine lung development and human lung tumor formation. Finally, we examined the formation of teratocarcinomas, embryonic cancers, to understand how dysregulation of the embryonic environment leads to tumor formation. We identified 3 gene methylation events by Restriction Landmark Genome Scanning that may play a role in teratocarcinoma development from embryonic stem cells. We performed microarray gene expression analysis on the tissues to determine expression changes taking place during transformation. Our study yielded 20 genes that have common expression pattern changes between ES cell cultures and teratocarcinoma cell lines, and between ES cell tumors and teratocarcinomas. The studies presented above have uncovered novel pathways involved in murine lung development, murine lung carcinogenesis, and embryonic tumor formation. These pathways have helped to further characterize lung carcinogenesis.
Ming You (Advisor)
201 p.
lung development; lung cancer; tumorigenesis; oligonucleotide microarray; teratocarcinoma; RLGS

Recommended Citations

Citations

  • Bonner, A. E. (2004). Organ development and tumorigenesis: a molecular link [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1073936508

    APA Style (7th edition)

  • Bonner, Allison. Organ development and tumorigenesis: a molecular link. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1073936508.

    MLA Style (8th edition)

  • Bonner, Allison. "Organ development and tumorigenesis: a molecular link." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1073936508

    Chicago Manual of Style (17th edition)

osu1073936508
1,260
© 2004, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.