15-Lipoxygenase-2 (ALOX15B) is an arachidonic acid metabolizing enzyme that has been implicated as a functional tumor suppressor for prostate cancer. The expression and activity of 15-LOX-2 are frequently suppressed during carcinogenesis of prostate, lung, esophageal and sebaceous gland. Based on the observations that restoration of 15-LOX-2 expression in prostate cancer cells inhibited both DNA replication and tumor development, 15-LOX-2 has been proposed as a functional tumor suppressor for prostate cancer. However, it is unknown how 15-LOX-2 expression and functionality are suppressed in cancerous cells, the mechanism involved for 15-LOX-2 to suppress tumor formation, and whether or not 15-LOX-2 can be utilized as a therapeutic agent or an effector to attenuate or inhibit the disease progression. Our long term goal is to elucidate the role of 15-LOX-2 in prostate cancer and to develop targeted approach for prevention and treatment of cancer. The specific hypothesis behind the proposed research is that 15-LOX-2 is a major regulatory switch controlling tumor dormancy, and that loss of 15-LOX-2 contributes to prostate carcinogenesis.
The specific aims are: 1) to characterize ALOX15B mutations/polymorphisms in human prostate cancer using mutational and sequencing analysis of human ALOX15B loci in prostate tumor cells;2) to determine the functionality of tumor cell (tc)-15-LOX-2 in prostate cancer biology through a gain of function by expression of recombinant tc-15-LOX-2 protein or loss of function by ablation of endogenous expression of tc-15-LOX-2 using RNAi approach;and 3) to delineate the mechanistic link between 15-LOX-2 and VEGF expression using promoter deletion and mutation analysis. The proposed studies will significantly advance our understanding about 15-LOX-2, a functional tumor suppressor, in prostate cancer biology. The proposed studies will lead to a better understanding of the loss of 15-LOX-2 functionality as a tumor suppressor during prostate carcinogenesis, and the mechanism by which 15-LOX-2 keeps tumor suppressed.

Public Health Relevance

15-Lipoxygenase-2 (ALOX15B) is a newly identified functional tumor suppressor whose functionality is frequently suppressed in prostate cancer. The goals of this proposal are to examine the mutations/polymorphisms of 15-LOX-2 gene loci, to determine the routes of 15-LOX-2 suppression in prostate cancer, and to elucidate how 15-LOX-2 keeps prostate tumor suppressed in a latent stage. The studies will improve the risk assessment, detection, prevention, and treatment of prostate cancer, a major threat to public health and a financial burden to Medicare.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Cancer Etiology Study Section (CE)
Program Officer
Yassin, Rihab R,
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Southern Illinois University School of Medicine
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Boral, Debasish; Nie, Daotai (2012) Cancer stem cells and niche mircoenvironments. Front Biosci (Elite Ed) 4:2502-14
Robbins, Gregory T; Nie, Daotai (2012) PPAR gamma, bioactive lipids, and cancer progression. Front Biosci (Landmark Ed) 17:1816-34
Malik, Babar; Nie, Daotai (2012) Cancer stem cells and resistance to chemo and radio therapy. Front Biosci (Elite Ed) 4:2142-9
Tang, Yong; Chen, Yakun; Jiang, Hongmei et al. (2010) Promotion of tumor development in prostate cancer by progerin. Cancer Cell Int 10:47
Yang, Dianer; Wang, Man-Tzu; Tang, Yong et al. (2010) Impairment of mitochondrial respiration in mouse fibroblasts by oncogenic H-RAS(Q61L). Cancer Biol Ther 9:122-33
Nie, Daotai (2010) Cancer stem cell and niche. Front Biosci (Schol Ed) 2:184-93
Zhang, Xuejing; Nie, Daotai; Chakrabarty, Subhas (2010) Growth factors in tumor microenvironment. Front Biosci (Landmark Ed) 15:151-65
Tang, Yong; Wang, Man-Tzu; Chen, Yakun et al. (2009) Downregulation of vascular endothelial growth factor and induction of tumor dormancy by 15-lipoxygenase-2 in prostate cancer. Int J Cancer 124:1545-51
Chen, Yakun; Tang, Yong; Chen, Shuqing et al. (2009) Regulation of drug resistance by human pregnane X receptor in breast cancer. Cancer Biol Ther 8:1265-72
Walia, Vijay; Ding, Ming; Kumar, Sumit et al. (2009) hCLCA2 Is a p53-Inducible Inhibitor of Breast Cancer Cell Proliferation. Cancer Res 69:6624-32