Stem Cell Regulation by the NF2 Tumor Suppressor Merlin

NF2 肿瘤抑制因子 Merlin 的干细胞调节

• 批准号: 7474689
• 负责人: Andrew B. Gladden
• 金额: $ 4.88万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474689
• 关键词: Ablation; Adherens Junction; Adult; Cancer Biology; Carcinogens; Cell Communication; Cell Proliferation; Cells; Communication; Contact Inhibition; Cytoskeleton; Data; Development; Disseminated Malignant Neoplasm; Employee Strikes; Epidermal Growth Factor Receptor; Epithelial; Genes; Human; In Vitro; Incidence; Intestines; Laboratories; Liver; Malignant Neoplasms; Mediating; Membrane; Metastatic Lesion; Molecular; Mus; Mutant Strains Mice; Neurofibromatosis 2; Neurofibromin 2; Notch Signaling Pathway; Phenotype; Process; Proteins; Receptor Signaling; Regulation; Role; Signal Transduction; Skin; Skin Carcinogenesis; Skin Neoplasms; Stem cells; Stimulus; Surface; Testing; Tissues; Tumor Suppressor Proteins; bone; extracellular; in vivo; keratinocyte; mouse model; notch protein; programs; receptor; receptor binding; stem; transcription factor; tumor; tumor initiation; tumorigenesis

DESCRIPTION (provided by applicant): Stem cells are maintained within the adult body in microenvironments that regulate both the differentiation and proliferation of these cells. The role that stem cells have in cancer development is poorly understood but critically important in normal and cancer biology. Our preliminary observations indicate that in vivo ablation of the Nf2 tumor suppressor, Merlin in the skin alters normal epidermal development. Therefore we hypothesize that Merlin is required for normal regulation of epithelial stem cells. Our long term objectives are: 1)To determine the role of Merlin in regulation of the epidermal stem cell compartment. 2)To determine whether Merlin organizes membrane receptor signaling in the epidermal stem cell niche. 3)To determine whether Nf2 deficiency promotes epidermal tumorigenesis. We have generated mice specifically deleting the Nf2 gene from mouse skin. We will utilize these mice in addition to molecular approaches to investigate the role of Merlin in the stem cell compartment. These studies will contribute to our understanding of how the Nf2 tumor suppressor regulates cell-cell interactions specifically between stem cells and the surrounding niche and the role these interactions have in tumor development and progression into metastatic cancer.

描述（由申请人提供）：干细胞维持在成人体内的微环境中，调节这些细胞的分化和增殖。干细胞在癌症发展中的作用知之甚少，但在正常和癌症生物学中至关重要。我们的初步观察表明，在体内消融的Nf 2肿瘤抑制因子，梅林在皮肤改变正常的表皮发育。因此，我们假设Merlin是上皮干细胞正常调节所必需的。我们的长期目标是：1）确定Merlin在调节表皮干细胞区室中的作用。2）确定Merlin是否在表皮干细胞龛中组织膜受体信号传导。3）确定Nf 2缺陷是否促进表皮肿瘤发生。我们已经产生了从小鼠皮肤中特异性删除Nf 2基因的小鼠。我们将利用这些小鼠，除了分子方法来研究梅林在干细胞隔室的作用。这些研究将有助于我们理解Nf 2肿瘤抑制因子如何调节干细胞与周围小生境之间的细胞-细胞相互作用，以及这些相互作用在肿瘤发展和进展为转移性癌症中的作用。