Prostate cancer accounts for 20 percent of all male malignancies and 11 percent of cancer deaths in men in the United States. The pathogenesis of converting prostatic intraepithelial neoplasia (PIN) to invasive carcinoma remains obscure. The long- term goal of the proposed research is to identify stage-specific gene markers and develop automated diagnosis which will facilitate early prostate cancer detection and enhance a physician's ability to make decisions on treatment. The hypotheses to be tested are (a) cell-specific, full-length cDNA libraries from prostate cells of known pathological changes from biopsied sections, cytology specimens, micro-metastasis, etc. can be generated; (b) genes which have been identified to be involved in prostatic cancer can be identified in the generated full- length cDNA libraries, and (c) Differential expression of stage- specific gene markers can be identified in different stage- specific cDNA libraries. Our immediate goal is to generate cDNA libraries from stage-specific human prostatic cancer cells obtained from histological sections; then, we will assess the quality of the cDNA libraries by confirming the full-length of a set of genes of known size and to establish the optimal condition to generate high quality cDNA libraries; we will examine differential expression of known genes of cDNA libraries generated from these stage-specific cells and identify gene markers using microarray technology as well as correlate the differentially expressed molecular markers to different stages of prostate cancer. This proposed research is worthwhile because, to this day, microarray technologies in prostate cancer have been either based on cDNA generated from xenografts and/or fluorescence in site hybridization (FISH). However, the P.I.'s laboratory has reported a newly-developed novel method of generating cell-specific full-length cDNA libraries from single cells and a laser-assisted preparation of single cells from human prostatic cancer histological slides. In this way, amplified messenger RNA libraries from a few tissue cells can provide molecular gene expression profiles at high resolution and in vivo analyses of cancerous gene expression in human prostate cancers is potentially feasible. These results may pave the way for a precise gene-chip diagnosis of stage-specific markers of human prostate cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA085722-03
Application #
6691035
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Kagan, Jacob
Project Start
2002-01-18
Project End
2006-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
3
Fiscal Year
2004
Total Cost
$365,625
Indirect Cost
Name
University of Southern California
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Lin, Shi-Lung; Chang, Donald; Chiang, Angela et al. (2008) Androgen receptor regulates CD168 expression and signaling in prostate cancer. Carcinogenesis 29:282-90
Lin, Shi-Lung; Kim, Hoon; Ying, Shao-Yao (2008) Intron-mediated RNA interference and microRNA (miRNA). Front Biosci 13:2216-30
Lin, Shi-Lung; Chiang, Angela; Chang, Donald et al. (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA 14:417-24
Ying, Shao-Yao; Chang, Donald C; Lin, Shi-Lung (2008) The microRNA (miRNA): overview of the RNA genes that modulate gene function. Mol Biotechnol 38:257-68
Lin, Shi-Lung; Chang, Donald; Ying, Shao-Yao (2007) Hyaluronan stimulates transformation of androgen-independent prostate cancer. Carcinogenesis 28:310-20
Lin, Shi-Lung; Chang, Donald C; Ying, Shao-Yao (2006) Isolation and identification of gene-specific microRNAs. Methods Mol Biol 342:313-20
Lin, S-L; Chang, S-Je; Ying, S-Y (2006) First in vivo evidence of microRNA-induced fragile X mental retardation syndrome. Mol Psychiatry 11:616-7
Ying, Shao-Yao; Chang, Donald C; Miller, Joseph D et al. (2006) The microRNA: overview of the RNA gene that modulates gene functions. Methods Mol Biol 342:1-18
Lin, Shi-Lung; Chang, Shin-Ju E; Ying, Shao-Yao (2006) Transgene-like animal models using intronic microRNAs. Methods Mol Biol 342:321-34
Ying, Shao-Yao; Lin, Shi-Lung (2006) Current perspectives in intronic micro RNAs (miRNAs). J Biomed Sci 13:5-15

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