Date of Award

4-19-2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Scott H. Garrett

Abstract

Prostate cancer is a leading cause of death among men world wide; while prostate cancer has many factors leading to its development; one such factor is cadmium exposure. Cadmium is a known human carcinogen and is an environmental factor that has been linked with prostate cancer progression. Metallothionein (MT) is a cadmium binding protein that is expressed within human tissues that may play a role in prostate carcinogenesis. Zinc is an important metal within the body and the prostate contains high levels of this metal within the cytosol of the cells, whereas the prostate cancer cells do not retain this feature; this change in zinc accumulation may be in part due to differential expression of the zinc transporter proteins within the prostate cells. This study examined the RWPE-1, a non-tumorgenic adult prostate cell line, to determine if it is a useful model system for studying metallothionein and zinc transporter genes expression and their relationship within the prostate and prostate cancer. The mRNAs of metallothionein and the zinc transporters Will be measured by real-time PCR and the MT-1/2 protein level Will be measured by immuno-dot blot and MALDI-TOF/TOF mass spectrometry. It was shown that the RWPE-1 cell line can be used as a model system in which to elucidate the mechanisms underlying the alterations of MT-1/2 expression that occur during the development of prostate cancer; it was also shown that RWPE-1 can be used to study zinc transporter expression within prostate cancer. RWPE-1 cells respond to Cd+2 and Zn+2 exposures by increasing the expression of MT-1/2 protein; it was also shown that calcium concentration of the growth media can alter the expression of MT-1/2 within RWPE-1 cells. Finally, 14 of the 19 zinc transporters were shown to be expressed within the RWPE-1 cells and that there is similar expression of zinc transporters in the RWPE-1 when compared to the tissue samples indicating that RWPE-1 can be a model system studying zinc transporter expression in relation to malignant transformation of the prostate.

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