(PQA2) MAMMALIAN REGENERATION, HIGH FAT DIETS, AND BREAST CANCER: A COMMON LINK?

(PQA2) 哺乳动物再生、高脂肪饮食和乳腺癌：共同的联系？

• 批准号: 8722513
• 负责人: Ellen s. Heber-Katz
• 金额: $ 12.36万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-16 至 2014-10-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8722513
• 关键词: Ablation; Address; Adipocytes; Adult; Autoimmunity; Biological Assay; Breast Cancer Cell; Breast Cancer Model; Candidate Disease Gene; Cell Communication; Cell Proliferation; Cells; Chromosome Mapping; Chronic; Coculture Techniques; Complex; Diet; Endothelial Cells; Environment; Etiology; FABP4 gene; Fat-Restricted Diet; Fatty acid glycerol esters; Female; Genes; Genetic; Goals; Growth; Human; Immune response; Immunocompetent; In Vitro; Inbred BALB C Mice; Inflammation; Inflammatory; Injection of therapeutic agent; LG/J Mouse; Laboratories; Lead; Link; MRL/MpJ Mouse; Malignant Neoplasms; Mammary Neoplasms; Measures; Modeling; Molecular; Mouse Strains; Mus; Natural regeneration; Neoplasm Metastasis; Newts; Obesity; PECAM1 gene; PTPRC gene; Parents; Phenotype; Population; Predisposition; Primary Neoplasm; Regulation; Resolution; Role; Site; Stromal Cells; Study Subject; System; Therapeutic; Tissues; Tumor Immunity; Tumor-Derived; Vascularization; Work; Wound Healing; angiogenesis; base; blastema; cancer cell; cancer therapy; cell growth; diet and cancer; feeding; fibroblast-activating factor; implantation; in vivo; inflammatory marker; innovation; insight; malignant breast neoplasm; mouse model; neoplastic cell; novel; oil red O; public health relevance; rapid growth; regenerative; response; tumor; tumor growth; tumor microenvironment; tumorigenesis

DESCRIPTION (provided by applicant): Obesity, often the result of a high fat diet, leads to chronic inflammation and stromal cell proliferation. In this application, we will address the issue of how a high fat diet leads to enhanced tumor cell growth and approach this from a previously unexplored direction. Examination of an adult mammalian regeneration model employing the MRL/MpJ mouse studied for its susceptibility to autoimmunity, obesity, and enhanced wound healing abilities, displays multiple phenotypes similar to the tumor microenvironment and has been the subject of study in the Heber-Katz laboratory for over a decade. The mapping of genes in this mouse has led to the identification of a novel gene signature defined by a small subset of genes which are regulated by a high fat diet in a sexually dimorphic fashion. The genes that constitute this so-called "high fat-selected regeneration-associated" or HFSRA gene signature are the basis of the proposed approach to defining the mechanistic basis for the association between a high fat diet and breast cancer. This approach is strongly supported by results demonstrating that these same genes are similarly expressed in human breast cancer-derived stromal cells. These studies will utilize the 4T1 orthotopic mouse breast cancer model in syngeneic BALB/c mice in vivo. In vitro studies will be carried out using 3D-culture systems relevant to the tumor microenvironment based on an understanding of the complexities of the tumor microenvironment and the host response to tumors, ranging from the role of stromal cells, inflammation and vascularization to tumor immunity, and is the focus of the Pur¿ laboratory. Working together as a team, the combined expertise of Drs. Heber-Katz and Pur¿ render the important but complex goals of this project eminently feasible.

描述（由申请人提供）：肥胖通常是高脂肪饮食的结果，导致慢性炎症和间质细胞增殖。在这个应用程序中，我们将解决这个问题