Advisory Committee Chair
Andra R Frost
Advisory Committee Members
Martin R Johnson
Rosa Serra
Danny R Welch
Bradley K Yoder
Andra R Frost
Document Type
Dissertation
Date of Award
2010
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen Receptor α (ERα)-negative breast cancer through tissue microarray analysis of 171 infiltrating breast cancers and in vitro cell culture studies. Furthermore, the role of Gli1 was investigated using ERalpha;-negative breast cancer cell lines and an experimental metastasis model. The result strongly supports that Gli1 promotes metastasis of MDA-MB-231(231) breast cancer cells and enhances migration and invasion of two ERalpha;-negative breast cancer cell lines via up-regulation of MMP-11. Taken together, these findings identify Gli1 as a promising target for treatment of ERalpha;-negative breast cancers.
Recommended Citation
Kwon, Yeon-Jin, "The Role of Gli1 in ERalpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, and Metastasis" (2010). All ETDs from UAB. 2195.
https://digitalcommons.library.uab.edu/etd-collection/2195