Award Date

1-1-2008

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Committee Member

Bryan Spangelo

Number of Pages

70

Abstract

Although there have been many research advances in the treatment and prevention of cancer, it remains a leading cause of death each year throughout the world. A major obstacle in the treatment of cancer is encountered when the cancer develops resistance to chemotherapeutic agents. To better understand resistance and identify biomarkers we propose to develop resistance in breast adenocarcinoma cancer cell lines, MDA-MB-231 and MCF-7, using common chemotherapeutic agents, doxorubicin and cisplatin. Microarray analysis will be preformed to identify over expression of proteins in these resistant lines. We hypothesize that genes which are over-expressed in a resistant cancer cell line may be responsible for the observed chemoresistance. To test this hypothesis, chemical inhibitors will be used to suppress protein expression in resistant and wild type cell lines, and then perform proliferation and viability assays to observe changes in protein synthesis from over expressed genes; Our preliminary results indicated 10 genes which were highly over-expressed in the resistant cancer cell line SD231RD2 in comparison to the MDA-MB-231 wild type cell line. We chose to focus on two genes, reported in the literature to be commonly expressed in response to stress, resulting in increased production of cyclooxygenase-2 (COX-2) and metalloproteinase-3 (MMP-3). Inhibition of COX-2 protein with indomethacin using clonogenic survivals reversed chemoresistance in resistant cells.

Keywords

Biomarkers; Breast cancer; Cancer; Chemotherapeutic; Determining; Drug; Protein; Resistance

Controlled Subject

Oncology; Biochemistry; Molecular biology

File Format

pdf

File Size

1536 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

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