Date of Award

2016

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Dianzheng Zhang, Advisor

Second Advisor

Cathy Hatcher

Third Advisor

Ruth Borghaei

Abstract

Prostate cancer, or prostatic carcinoma (PrCa), is the second leading cause of cancer-related deaths in men in the Western world. One in seven men are expected to be diagnosed with the disease in the United States. Suppressing androgen/androgen receptor pathway is a first-line therapeutic treatment known as Androgen Deprivation Therapy (ADT). Most patients respond well to ADT, but an overwhelming majority of PrCa progress to an advanced stage of PrCa independent of hormone, known as Castration Resistant Prostate Cancer (CRPC). There is currently no known cure for CRPC. In this study, the androgensensitive LNCaP cells served as an in vitro model of ADT. LNCaP cells were grown without hormone for twenty days and were collected every two days; the levels of AR protein and its target gene PSA mRNA were examined over this interval. Full-length AR protein levels appear to remain unchanged throughout the twenty days, but hormone withdrawal leads to lower PSA levels. In addition, we also observed the effects of hormonal withdrawal on cell morphology; LNCaP cells adapted a shape resembling neuronal cells with long and slender connections between them. Furthermore, the appearance of truncated AR isoforms occurred during the extended hormonal withdrawal. These findings suggest that hormonal withdrawal not only suppresses AR activity without affecting AR protein levels in prostate cancer calls, but also results in the morphological change.

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