Type
Text
Type
Dissertation
Advisor
Powers, Scott | Crawford, Howard | Egeblad, Mikala | Wigler, Michael | Mittal, Vivek
Date
2012-05-01
Keywords
Genetics--Oncology | Breast cancer, Microenvironment, tumor-stromal interactions
Department
Department of Genetics
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/71056
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
There is increasing evidence that cancers develop as aberrant tissues with co-evolving tumor and surrounding non-malignant cells rather than from a single aberrant cell that has undergone multiple genetic alterations. As a result, different cellular components of the tumor mass are involved in a highly complex molecular crosstalk. However, all of the underlying molecular mechanisms of these interactions are not fully identified. Here, I have used genome-wide analysis to identify genes that mediate functional interactions between breast cancer cells and fibroblasts using a model system that allows for both genomic analysis and genetic manipulation of epithelial and stromal compartments. I've established through extensive bioinformatics analysis that this system reflects stromal alterations that occur in human primary breast cancers. RNAi analyses and a co-injection tumorigenicity assay were used to functionally validate genes involved in breast epithelial-stromal fibroblast interactions. I found that the majority of the genes surveyed mediated significant yet diverse roles in promoting cancer in vivo. Previous functional analyses have emphasized single genes or single processes as being the key players in tumor-promoting properties of fibroblasts but did not take a systematic genome-wide approach. Our results indicate there are instead multiple genes and processes involved in fibroblast promotion of breast cancer, providing multiple targets for therapeutic inhibition. | 190 pages
Recommended Citation
Rajaram, Megha, "Functional Genomic Identification of Multiple Targets for Inhibiting Tumor-Promoting Fibroblasts" (2012). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 263.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/263