All ETDs from UAB

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.

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