ACVP > 2004 ACVP Christopher T. Starost Memorial Oncology Scholarship

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2004 ACVP Christopher T. Starost Memorial Oncology Scholarship

2005 Christopher T. Starost Memorial Oncology Scholarship Abstracts

First Place

SODIUM/IODIDE SYMPORTER REGULATION BY tRA, FORSKOLIN, RAS AND PI3K IN MCF-7 HUMAN BREAST CANCER CELLS. K.A.B. Knostman1, Z. Zhang2, C. C. Capen1, S.M. Jhiang3 1. Department of Veterinary Biosciences, 2 Ohio State Biochemistry Program, and 3 Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH.

The sodium/iodide symporter (NIS) is a membrane glycoprotein expressed in the thyroid gland and lactating mammary gland. NIS mediates radioiodide imaging and therapeutic ablation of thyroid carcinomas with potential for similar use in breast cancer treatment, as most human breast tumors express NIS. Less is known about the regulation of NIS expression in the mammary gland than in the thyroid. We have identified ras, PI3K and cAMP as potentially important in NIS upregulation in mouse models of breast cancer. MCF-7 human breast cancer cells respond to all-trans-retinoic acid (tRA) with modest NIS expression and radioiodide uptake. In this study, we demonstrated that MCF-7 cells expressing v-Ha-ras or PI3K p110 express significant hypoglycosylated cytoplasmic NIS protein and lack radioiodide uptake. Treatment of MCF-7 cells with tRA leads to NIS expression in less than 10% of cells, but the NIS protein is heavily glycosylated, efficiently trafficked to the cell surface, and functional. Treatment of MCF-7 cells with combined tRA and forskolin leads to a synergistic increase in NIS protein and radioiodide uptake, resulting from an increase in NIS protein in responding cells with no change in the percentage of cells responding. Magnetic antibody cell sorting is underway to isolate MCF-7 cells responding to tRA for analysis of expression levels of RA receptors and related transcription factors, global gene microarray and proteomics analysis. Future studies on NIS regulation in mouse mammary carcinoma cells will include investigation into mechanisms accounting for the lack of radioiodide uptake in certain cells expressing significant NIS protein.

Second Place:

THE EFFECT OF POLYUNSATURATED FATTY ACIDS ON PROSTATIC ADENOCARCINOMA DEVELOPMENT IN THE PROSTATE-SPECIFIC PTEN KNOCKOUT MURINE MODEL. D. L. Perry1, Y. Chen2, M. Cline1. 1.Department of Pathology Section of Comparative Medicine, 2; Cancer Biology, Wake Forest University School of Medicine, NC.

The tumor suppressor gene PTEN is frequently mutated in human prostate cancer. Numerous PTEN knockout models have been developed in an attempt to closely mimic disease progression and the lesions seen in the human disease. This study utilizes a prostate-specific PTEN Cre-mediated knockout murine model to determine the effect of polyunsaturated fatty acids on prostate cancer development. Mice were fed three different custom diets composed of varying ratios of omega 3 to omega 6 fatty acids. These diets contained fatty acid ratios that corresponded to a traditional Western diet (1 n-3:20 n-6), a high omega 3 diet (1:1), and a high omega 6 diet (1:40). The wild-type, PTEN heterozygous, and PTEN homozygous knockout mice were sacrificed at 5, 8, and 12 weeks of age. Organ weights and histopathologic examination of the prostate tissues followed. Diet, genotype, and age had profound and significant effects on prostate weight (p less than 0.005). PTEN homozygous animals at 12 weeks of age consuming a high omega 6 diet had a 30% increase in prostate weight in contrast to mice consuming the high omega 3 diet, which had a 16% decrease in prostate weight. The highest numbers of invasive carcinomas were seen in 12 week old PTEN homozygous knockout mice consuming the omega 6 rich diet. There were significant interactions between genotype and age and genotype and diet. This prostate specific model demonstrates that fatty acid ratios can affect the progression of prostatic neoplasms.

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