Our broad objectives are to elucidate and to understand the mechanism by which the prostate gland performs the unique function of accumulating and secreting extraordinarily high levels of citric acid. Of particular importance is elucidation of the role of hormones in the regulation of prostate citrate production. In humans, prostatic neoplasms constitute the most prevalent neoplastic disease in man. Benign prostatic hypertrophy and prostatic carcinoma are characterized by major alterations in the ability to produce citrate. These studies will lead to the eventual understanding of the transformation of normal prostate cells to neoplastic cells and might provide a rational approach to the use of hormonal-related agents in the management of these neoplasms. This project focuses on the role of prolactin in the regulation of citrate production by lateral prostate of the rat. The lateral prostate is homologous to the lateral lobe of the human prostate. The studies will elucidate the effect of prolactin on citrate synthesis and citrate oxidation, and the mechanisms by which prolactin regulates citrate production. The program will elucidate the interaction among prolactin-zinc-citrate oxidation in prostate. Studies will also determine the mechanism by which prolactin regulates gene action associated with citrate synthesis. A comparative study with pig prostate will be conducted which will provide corroborating evidence that these relationships are likely applicable to human prostate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042839-03
Application #
2142581
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1992-03-01
Project End
1996-02-29
Budget Start
1994-03-01
Budget End
1995-02-28
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Physiology
Type
Schools of Dentistry
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Costello, Leslie C (2018) Poor Science; Poorly Trained Scientists; Poor Policies: Major Deterrents to the War on Cancer. J Can Res Updates 7:79-83
Costello, Leslie C; Franklin, Renty B (2017) Decreased zinc in the development and progression of malignancy: an important common relationship and potential for prevention and treatment of carcinomas. Expert Opin Ther Targets 21:51-66
Franklin, Renty B; Zou, Jing; Zheng, Yao et al. (2016) Zinc Ionophore (Clioquinol) Inhibition of Human ZIP1-Deficient Prostate Tumor Growth in the Mouse Ectopic Xenograft Model: A Zinc Approach for the Efficacious Treatment of Prostate Cancer. Int J Cancer Clin Res 3:
Costello, Leslie C; Franklin, Renty B (2016) A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Arch Biochem Biophys 611:100-112
Costello, Leslie C; Zou, Jing; Franklin, Renty B (2016) In situ clinical evidence that zinc levels are decreased in breast invasive ductal carcinoma. Cancer Causes Control 27:729-35
Costello, Leslie C; Franklin, Renty B; Zou, Jing et al. (2015) Evidence that Human Prostate Cancer is a ZIP1-Deficient Malignancy that could be Effectively Treated with a Zinc Ionophore (Clioquinol) Approach. Chemotherapy (Los Angel) 4:
Franklin, Renty B; Zou, Jing; Costello, Leslie C (2014) The cytotoxic role of RREB1, ZIP3 zinc transporter, and zinc in human pancreatic adenocarcinoma. Cancer Biol Ther 15:1431-7
Costello, Leslie C; Franklin, Renty B (2014) The status of zinc in the development of hepatocellular cancer: an important, but neglected, clinically established relationship. Cancer Biol Ther 15:353-60
Costello, Leslie C; Franklin, Renty B (2013) A Review of the Current Status and Concept of the Emerging Implications of Zinc and Zinc Transporters in the Development of Pancreatic Cancer. Pancreat Disord Ther Suppl 4:
Costello, Leslie C; Franklin, Renty B (2013) A review of the important central role of altered citrate metabolism during the process of stem cell differentiation. J Regen Med Tissue Eng 2:

Showing the most recent 10 out of 37 publications