FATTY ACIDS AND PPARS IN BREAST CANCER PREVENTION

脂肪酸和 PPAR 预防乳腺癌

• 批准号: 6853606
• 负责人: LISA D YEE
• 金额: $ 6.63万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-09 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6853606
• 关键词: athymic mouse; breast neoplasms; cancer prevention; clinical research; dietary lipid; fatty acid metabolism; fatty acids; female; gene expression; human subject; neoplastic process; nutrition related neoplasm /cancer; nutrition related tag; peroxisome proliferator activated receptor; prostaglandins; vascular endothelial growth factors; women' s health

Breast cancer remains the second leading cause of cancer death of women in the United States. Preventive measures with minimal adverse effects are needed to reduce the incidence and progression of breast cancer. The long-term research goal of the principal investigator, Dr. Yee, is to investigate the molecular mechanisms of breast cancer progression and ultimately develop new interventions for breast cancer prevention and eradication. Dr. Yee is requesting funds to develop her skills in breast cancer prevention and control, an effort that will complement her training as a surgeon specializing in breast cancer and allow her to conduct the future translational research vital to reducing breast cancer risk. Her training in preventive oncology will encompass mentorship by select faculty of The Ohio State University, Comprehensive Cancer Center and James Cancer Hospital and Solove Research Institute, combining didactic course work and a cancer prevention research project. The plan integrates molecular genetics, nutritional sciences, and clinical breast cancer research. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that stimulate transcriptional activity in response to ligands such as fatty acids and prostaglandins. The PPARgamma subtype regulates cell differentiation and proliferation in normal and malignant tissues. Cell culture and animal models will be used to evaluate fatty acid effects on PPARgamma activation in breast cancer. Human breast tumors and surrounding fat and epithelial tissue will also be assessed for patterns of expression of PPARs and other factors affecting PPAR activation. This work will serve to generate data to support a prospective clinical study of the effects of dietary fat and PPARgamma on breast cancer progression. Combined with a didactic course of study in a stimulating scientific and clinical environment, this project will give Dr. Yee the training required to become an independent clinician scientist in the field of preventive oncology.

乳腺癌仍然是美国妇女癌症死亡的第二大原因。 需要采取副作用最小的预防措施，以减少乳腺癌的发病率和进展。 主要研究者Yee博士的长期研究目标是研究乳腺癌进展的分子机制，并最终开发预防和根除乳腺癌的新干预措施。Yee博士正在申请资金，以发展她在乳腺癌预防和控制方面的技能，这一努力将补充她作为乳腺癌专业外科医生的培训，并使她能够进行对降低乳腺癌风险至关重要的未来转化研究。 她在预防肿瘤学方面的培训将包括由俄亥俄州州立大学、综合癌症中心、詹姆斯癌症医院和Solove研究所的精选教师指导，结合教学课程和癌症预防研究项目。 该计划整合了分子遗传学、营养科学和临床乳腺癌研究。过氧化物酶体增殖物激活受体（PPARs）是核受体，其响应于配体（例如脂肪酸和胡萝卜素）而刺激转录活性。 PPARgamma亚型调节正常和恶性组织中的细胞分化和增殖。 细胞培养和动物模型将用于评价脂肪酸对乳腺癌中PPARgamma活化的影响。 还将评估人乳腺肿瘤和周围脂肪和上皮组织的PPARs表达模式和影响PPARs活化的其他因素。这项工作将有助于产生数据，以支持膳食脂肪和PPARgamma对乳腺癌进展的影响的前瞻性临床研究。 结合在刺激的科学和临床环境中的教学课程，该项目将为Yee博士提供成为预防肿瘤学领域独立临床科学家所需的培训。

项目成果

Dietary (n-3) polyunsaturated fatty acids inhibit HER-2/neu-induced breast cancer in mice independently of the PPARgamma ligand rosiglitazone.

• DOI: 10.1093/jn/135.5.983
• 发表时间: 2005-05
• 期刊: The Journal of nutrition
• 作者: L. Yee;D. Young;T. Rosol;A. Vanbuskirk;S. Clinton

The antiproliferative effects of PPARgamma ligands in normal human mammary epithelial cells.

PPARgamma 配体在正常人乳腺上皮细胞中的抗增殖作用。

• DOI: 10.1023/a:1022978608125
• 发表时间: 2003
• 期刊: Breast cancer research and treatment
• 影响因子: 3.8
• 作者: Yee,LisaD;Guo,Yan;Bradbury,Jamie;Suster,Saul;Clinton,StevenK;Seewaldt,VictoriaL
• 通讯作者: Seewaldt,VictoriaL