Date of Degree

5-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biology

Advisor

Marieke O. Burleson

Advisor

Russell Raymond

Abstract

When cells of the prostate gland start growing uncontrollably, it results in cancer due to genetic aberrations. The development and progression of prostate cancer depend on androgenic stimulation. Although prostate cancer is temporarily treated by depriving a tumor of androgen, the patient relapses getting a castration-resistant form of the disease called castration-resistant prostate cancer (CRPC). CRPC can specifically develop through crosstalk of androgen receptor signalling pathways. One such pathway that is of specific interest in this paper is the MED12 regulated SHH signalling pathway. The mediator is a signal processor that helps in the transduction of gene-specific transcription factors to RNA Polymerase II (Pol II). The activation of SHH ligand activates a transcription factor called GLI3 which physically targets the MED12 interface within the mediator complex so as to functionally reverse mediator dependent suppression of SHH target gene transcription. In this paper, we have shown that MED12 expression is critical in regulating androgen independent prostate cancer cell and therefore progression towards CRPC. Also, GLI3-dependent SHH signalling is indeed required for the progression of MED12 mutated prostate cancer cells to CRPC, after castration.

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