The overall objective of this proposal is to identify molecular genetic mechanisms by which adult human non-neoplastic prostate epithelial cells are driven towards increasingly malignant phenotypes. Investigation of specific cytogenetic alterations found to be associated with the tumorigenic or metastatic capacity of SV40 large T antigen immortalized human prostate epithelial cells (SV40T PEC) in athymic nude mice provides a novel way to study mechanism of transformation. In this proposal, the hypothesis to be tested is that chromosomes 16 and/or 19 contain one or more genes that suppress tumorigenicity and/or metastasis.
The specific aims are: (1) to further delineate the minimal regions of loss of heterozygosity (LOH) occurring on chromosomes 16 and 19 as these cells progress; (2) to determine whether restoration of normal chromosome dosage by microcell mediated transfer of: (a) an intact normal human chromosome 16, or (b) chromosome 19 into appropriate clones will suppress tumor incidence, growth rate, and/or metastasis in athymic nude mice; (3) to exploit their unique system to identify the smallest areas on chromosomes 16 and/or 19 that harbor functional tumor suppressor activity. These studies will facilitate understanding of the most common tumor occurring among American men. This may lead to new opportunities for improved diagnosis, prognostic assessment, or therapeutic intervention for a disease having no satisfactory treatment options.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Yang, Shen K
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Virginia Commonwealth University
Schools of Medicine
United States
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Jackson-Cook, Colleen; Zou, Ying; Turner, Kristi et al. (2003) A novel tumorigenic human prostate epithelial cell line (M2205): molecular cytogenetic characterization demonstrates C-MYC amplification and jumping translocations. Cancer Genet Cytogenet 141:56-64
Dumur, Catherine I; Dechsukhum, Chavaboon; Ware, Joy L et al. (2003) Genome-wide detection of LOH in prostate cancer using human SNP microarray technology. Genomics 81:260-9
Liu, Xuhui; Wu, Yongzhong; Zehner, Zendra E et al. (2003) Proteomic analysis of the tumorigenic human prostate cell line M12 after microcell-mediated transfer of chromosome 19 demonstrates reduction of vimentin. Electrophoresis 24:3445-53
Dumur, Catherine I; Dechsukhum, Chavaboon; Wilkinson, David S et al. (2002) Analytical validation of a real-time reverse transcription-polymerase chain reaction quantitation of different transcripts of the Wilms' tumor suppressor gene (WT1). Anal Biochem 309:127-36
Akalin, A; Elmore, L W; Forsythe, H L et al. (2001) A novel mechanism for chaperone-mediated telomerase regulation during prostate cancer progression. Cancer Res 61:4791-6
Astbury, C; Jackson-Cook, C K; Culp, S H et al. (2001) Suppression of tumorigenicity in the human prostate cancer cell line M12 via microcell-mediated restoration of chromosome 19. Genes Chromosomes Cancer 31:143-55
Bae, V L; Jackson-Cook, C K; Maygarden, S J et al. (1998) Metastatic sublines of an SV40 large T antigen immortalized human prostate epithelial cell line. Prostate 34:275-82
Ware, J L (1998) Growth factor network disruption in prostate cancer progression. Cancer Metastasis Rev 17:443-7
Plymate, S S; Bae, V L; Maddison, L et al. (1997) Type-1 insulin-like growth factor receptor reexpression in the malignant phenotype of SV40-T-immortalized human prostate epithelial cells enhances apoptosis. Endocrine 7:119-24
Plymate, S R; Bae, V L; Maddison, L et al. (1997) Reexpression of the type 1 insulin-like growth factor receptor inhibits the malignant phenotype of simian virus 40 T antigen immortalized human prostate epithelial cells. Endocrinology 138:1728-35

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