Abstract

description) The focus of this grant proposal is to study how steroid hormones regulate the organization of DNA and nuclear structure in the prostate, and how the telomerase activity is modulated by androgens. The applicant has reported that nuclear matrix provides the three-dimensional structure of the nucleus and organizes the genome into topologically restrained DNA loops that are anchored at their base to the matrix. Active genes are in close proximity to the matrix and are bound to tissue-specific matrix protein that also binds to the nuclear androgen receptor facilitating transcription. The periphery of the matrix binds and organizes the telomeres of the chromosome. The applicant proposed a stem-cell model for normal and abnormal growth of the prostate. Study on the stem cell markers and their mechanism of action will provide important insight into the cell renewal balance in the prostate.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK022000-29
Application #
6329288
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Mullins, Christopher V
Project Start
1978-09-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2002-11-30
Support Year
29
Fiscal Year
2001
Total Cost
$304,573
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Urology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Takaha, Natsuki; Resar, Linda M S; Vindivich, Don et al. (2004) High mobility group protein HMGI(Y) enhances tumor cell growth, invasion, and matrix metalloproteinase-2 expression in prostate cancer cells. Prostate 60:160-7
Takaha, Natsuki; Hawkins, Anita L; Griffin, Constance A et al. (2002) High mobility group protein I(Y): a candidate architectural protein for chromosomal rearrangements in prostate cancer cells. Cancer Res 62:647-51
Lupold, Shawn E; Hicke, Brian J; Lin, Yun et al. (2002) Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Res 62:4029-33
De Marzo, A M; Nelson, W G; Meeker, A K et al. (1998) Stem cell features of benign and malignant prostate epithelial cells. J Urol 160:2381-92
De Marzo, A M; Meeker, A K; Epstein, J I et al. (1998) Prostate stem cell compartments: expression of the cell cycle inhibitor p27Kip1 in normal, hyperplastic, and neoplastic cells. Am J Pathol 153:911-9
Nardozza, T A; Quigley, M M; Getzenberg, R H (1996) Association of transcription factors with the nuclear matrix. J Cell Biochem 61:467-77
Luke, M C; Coffey, D S (1994) Human androgen receptor binding to the androgen response element of prostate specific antigen. J Androl 15:41-51
Murphy, B C; Pienta, K J; Coffey, D S (1992) Effects of extracellular matrix components and dihydrotestosterone on the structure and function of human prostate cancer cells. Prostate 20:29-41
Partin, A W; Steinberg, G D; Pitcock, R V et al. (1992) Use of nuclear morphometry, gleason histologic scoring, clinical stage, and age to predict disease-free survival among patients with prostate cancer. Cancer 70:161-8
Pienta, K J; Getzenberg, R H; Coffey, D S (1992) Characterization of nuclear morphology and nuclear matrices in ageing human fibroblasts. Mech Ageing Dev 62:13-24

Showing the most recent 10 out of 23 publications