Prostaglandin D and skin cancer prevention

前列腺素 D 与皮肤癌预防

• 批准号: 7388737
• 负责人: HENRY J LIN
• 金额: $ 6.57万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-24 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7388737
• 关键词: Anabolism; Blood; Blood Circulation; Chemicals; Chemoprevention; Chemopreventive Agent; Coupled; Data; Development; Dinoprostone; Enzymes; Flushing; GTP-Binding Proteins; Goals; Hand; Hematopoietic; Intestines; Knock-out; Knockout Mice; Langerhans cell; Lead; Malignant Neoplasms; Modeling; Mus; Nicotinic Acids; Organ; Pathway interactions; Production; Prostaglandin D2; Prostaglandin E Receptor; Prostaglandins; Prostaglandins D; Protein Overexpression; Publishing; Range; Research Personnel; Role; Route; Skin; Skin Cancer; Skin Neoplasms; TP53 gene; Transgenes; Transgenic Organisms; Translating; UV induced; United States; Work; adenoma; angiogenesis; cancer chemoprevention; cell growth; improved; insight; macrophage; monocyte; mouse model; prostaglandin R2 D-isomerase; receptor; research study; skin cancer prevention; tumor; tumor growth; tumorigenic; ultraviolet irradiation

DESCRIPTION (provided by applicant): Skin cancer is the most common cancer in the United States, with over 1,300,000 new cases per year. The overall goals are to understand how prostaglandin pathways influence development of skin tumors and use the information to improve cancer chemoprevention. The prostaglandin cascade makes prostaglandins E2, D2 (PGE2, PGD2), and other prostanoids. PGD2 promotes tumors in the skin and other organs. For bowel tumors, experiments showed that adenoma-prone ApcMin/+ mice had 50% more tumors when deficient in hematopoietic prostaglandin D synthase (H-PGDS). Conversely, mice had 70% fewer tumors, if they had a transgene causing high levels of H-PGDS. Thus, PGD2 production appears to suppress tumors. Niacin dramatically raises blood levels of PGD2 (causing flushing). The rise in PGD2 is due to the G-protein- coupled nicotinic acid receptor, which stimulates the prostaglandin cascade in Langerhans cells in the skin. Thus, the hypotheses are: (i) PGD2 production may suppress skin tumors, similar to the effect observed for bowel tumors and (ii) niacin may be a chemopreventive agent, due to niacin-responsive Langerhans cells in skin. The proposed experiments will manipulate PGD2 production and assess effects on a mouse model of skin cancer. Specific Aims are: (1) Define effects of H-PGDS transgenes and H-PGDS knockouts on UV-induced skin tumors in heterozygous p53 knockout mice; (2) define effects of dietary niacin on UV-induced skin tumors in heterozygous p53 knockout mice. Significance: Results should give new insight into roles and mechanisms of prostaglandins in tumor growth. Niacin as a booster of PGD2 may emerge as an agent to be studied for chemoprevention of skin cancer.

描述（由申请人提供）：