There is strong evidence that polypeptide growth factors such as transforming growth factor (TGFa), epidermal growth factor (EGF), and fibroblast growth factor (FGF) are involved in regulation of the growth of normal as well as abnormal prostate cells. Most of these growth factors mediate their signals through receptor-tyrosine kinases. Tyrosine kinases, while representing a minor population of protein kinases in the cell, play major roles in cellular growth, differentiation and apoptosis. Surprisingly, little is known about the tyrosine kinases expressed in prostate tissues and the growth signals they transmit. Built upon a significant amount of preliminary data, the investigator's experiences in receptor-tyrosine kinase and the coinvestigator's expertise in prostate organ culture, this application is intended to provide fundamental knowledge on the growth signals and tyrosine kinases expressed in normal and abnormal prostate cells. We have recently developed an effective approach to profile tyrosine kinases in a given cell, which has allowed us to describe most, if not all, of the tyrosine kinases in a prostate carcinoma. We wish to apply this approach to study and contrast the tyrosine kinase patterns in normal and abnormal prostate cells. One of the major aims is to identify novel and tissue-specific kinases in prostate tissues.
A second aim i s to use erbB/EGF receptor as a paradigm to study the crucial signal pathways involved in growth regulation of normal prostate cells. The """"""""cross-talk"""""""" between cytokine receptor and growth factor receptor will also be explored.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK052659-01
Application #
2018163
Study Section
Special Emphasis Panel (SRC (05))
Project Start
1997-07-24
Project End
2000-05-31
Budget Start
1997-07-24
Budget End
1998-05-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Guo, W; Liu, R; Bhardwaj, G et al. (2014) Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor. Cell Death Dis 5:e1409
Guo, Wenchang; Liu, Ruiwu; Bhardwaj, Gaurav et al. (2013) CTA095, a novel Etk and Src dual inhibitor, induces apoptosis in prostate cancer cells and overcomes resistance to Src inhibitors. PLoS One 8:e70910
Wang, L-Y; Kung, H-J (2012) Male germ cell-associated kinase is overexpressed in prostate cancer cells and causes mitotic defects via deregulation of APC/CCDH1. Oncogene 31:2907-18
Guo, Wenchang; Liu, Ruiwu; Ono, Yoko et al. (2012) Molecular characteristics of CTA056, a novel interleukin-2-inducible T-cell kinase inhibitor that selectively targets malignant T cells and modulates oncomirs. Mol Pharmacol 82:938-47
Kung, Hsing-Jien (2011) Targeting tyrosine kinases and autophagy in prostate cancer. Horm Cancer 2:38-46
Wu, Zhaoju; Chang, Pei-Ching; Yang, Joy C et al. (2010) Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors. Genes Cancer 1:40-49
Hsia, Datsun A; Tepper, Clifford G; Pochampalli, Mamata R et al. (2010) KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation. Proc Natl Acad Sci U S A 107:9671-6
Kung, Hsing-Jien; Evans, Christopher P (2009) Oncogenic activation of androgen receptor. Urol Oncol 27:48-52
Purnell, Phillip R; Mack, Philip C; Tepper, Clifford G et al. (2009) The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells. J Thorac Oncol 4:448-54
Kim, Randie H; Bold, Richard J; Kung, Hsing-Jien (2009) ADI, autophagy and apoptosis: metabolic stress as a therapeutic option for prostate cancer. Autophagy 5:567-8

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