Abstract

The overall objective of this proposal is to identify key mechanisms by which adult human non-neoplastic prostate epithelial cells are driven towards increasingly malignant phenotypes. Characterization of molecular and cytogenetic modifications which may correlate with the malignant potential of human prostate tumor cells will be undertaken. The following are the specific aims of this proposal: (10 To immortalize adult human non-neoplastic prostatic epithelial cells from in vitro by transfection of specific transforming genes of SV40 or Human Papilloma Viruses (HPV). Histopathologically confirmed nonneoplastic prostatic tissue obtained surgically will be the source of cells. (2) To drive these cells further toward complete tumorigenicity by exposure in vitro to chemical agents implicated in prostatic carcinogenesis. Emphasis will be placed upon the impact of treatment with both direct (MNNG, ) and indirect (benzo[a]pyrene) carcinogens. (3) At each stage of tumor evolution, the resulting cells will be characterized in terms of morphology, in vitro growth capacity, cytogenetics, and immunocytochemically detectable marker proteins (epithelial cytokeratins, prostate specific antigen, prostatic acid phosphatase, epidermal growth factor receptor, androgen receptor, etc.). In addition, tumorigenicity will be evaluated by ability to grow progressively as a tumor in athymic nude mice. (4) Insights into prostatic epithelial cell transformation generated by these experiments will be investigated for relevence to the natural history of human benign and malignant neoplasms. These studies will facilitate our understanding of the most common tumor occurring among American men, and thus may lead to new opportunities for therapeutic intervention in a disease for which there are no satisfactory treatment options.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA058126-03
Application #
2098816
Study Section
Special Emphasis Panel (SRC (70))
Project Start
1992-09-30
Project End
1997-07-31
Budget Start
1994-09-30
Budget End
1995-07-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298

  Publications

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
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
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
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

Showing the most recent 10 out of 19 publications