UMGCC Research Program:
Hormone Responsive Cancers Program
Contact
Information:
Mailing Address:
University of Maryland Dental School
4-E-36A
Baltimore, MD 21201
Email:
rbf001@dental.umaryland.edu
Phone:
410-706-7259
Fax:
410-706-7259
Research Interests:
The focus of our research is the biology of the prostate gland and prostate cancer. The prostate gland normally accumulates and secretes an extraordinarily high level of citric acid. In addition, the prostate also accumulates very high levels of zinc. These physiological functions of citrate and zinc accumulation are regulated by endocrine hormones, specifically testosterone and prolactin. A major area of interest in our laboratory is the molecular mechanisms by which these hormones regulate citrate production and zinc accumulation. These differentiated functions of citrate production and zinc accumulation are universally lost with the development of prostate cancer. Thus, we are interested in the metabolic alterations that account for the metabolic transformation that is associated with the development of prostate malignancy. Our work has established that zinc plays an important role in the normal function of the prostate. Zinc inhibition of mitochondrial aconitase is the mechanism whereby the prostate is capable of accumulating citrate. The lost of zinc accumulating ability is an early change in the progression to prostate cancer. A goal of our current research is to understand the molecular mechanism and regulation of zinc uptake by prostate cells and to determine if specific zinc transport molecules can be effective targets for therapy and/or diagnosis for prostate cancer. Another major focus is the signal transduction pathways that account for prolactin and testosterone regulation of the enzymes that are critical for citrate production and accumulation. Our work has shown that the prolactin effect on prostate metabolic enzymes involves activation of specific protein kinase C (PKC) isoforms in the prostate and that the activation of PKC results in activation of the transcription factor AP1. AP1 activation then increases the expression of metabolic genes that are important in the pathway of citrate production and accumulation.
Publications:
Franklin, R.B., Ma, J., Zou, J., Kukoyi, B.I., Feng, P., Costello, L.C. Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells. J. Inorganic Biochemistry 96(2-3): 435-442, 2003
Franklin, R.B., Zou, J., Ma, J., Costello, L.C. Protein kinase C epsilon and AP-1 mediate prolactin regulation of mitochondrial aspartate aminotransferase expression in the rat lateral prostate. Mol and Cell. Endocrin, 170:153-161, 2000.
Costello, L.C. and Franklin, R.B. The metabolism of prostate malignancy: Insight into the pathogenesis of prostate cancer and new approaches for its diagnosis and treatment. Oncology Spectrums 2:452-457, 2001.
Costello, L.C. and Franklin, R.B.. Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Horm. Metabol. Res. 34:417-424, 2002.
Feng, P. Li,T-L, Guan, Z-X, Franklin, R.B. Costello, L.C. Direst effect of zinc on mitochondrial apoptogenesis in prostate cells. The Prostate 52:311-318, 2002.
Gorski,E. Zou, J., Costello, L.C. and Franklin, R.B. Protein kinase C mediates prolactin regulation of mitochondrial aminotransferase gene expression in prostate cells. Molecular Urology 3:17-23, 1999.
Costello, L.C., Liu, Y., Zou, J. Franklin, R.B. Evidence for a zinc uptake transporter in human prostate cancer cells which is regulated by prolactin and testosterone. J. Biol. Chem. 274:17499-17504, 1999.
