Do NFATc2 and cJun Cooperate to Activate Transcription in Breast Cancer Cells?

NFATc2 和 cJun 是否协同激活乳腺癌细胞的转录？

• 批准号: 8706870
• 负责人: James Goodrich
• 金额: $ 7.55万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-25 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8706870
• 关键词: Address; Aftercare; Antigens; Applications Grants; Aromatic Polycyclic Hydrocarbons; Binding; Biochemical; Breast Cancer Cell; Breast Epithelial Cells; Cadmium; Calcium; Cancer Etiology; Cancer cell line; Carcinogens; Cell Cycle; Cell Line; Cell Nucleus; Cells; Cessation of life; ChIP-seq; Chemicals; Data; Development; Disease; Disease Progression; Environmental Carcinogens; Foundations; Future; Gene Expression; Genes; Genetic Transcription; Genome; Growth; Heavy Metals; Human; Immune response; Immunofluorescence Immunologic; Individual; Laboratories; Life; Malignant Neoplasms; Messenger RNA; Molecular; Monitor; Nuclear; Pilot Projects; Process; RNA Polymerase II; Research; Role; Sequence Analysis; Signal Transduction; T-Lymphocyte; Techniques; Testing; Time; Transcription Coactivator; Transcriptional Regulation; Western World; Woman; Work; base; biological systems; cancer cell; cancer invasiveness; cancer type; cell growth; cell motility; chemical carcinogen; insight; knock-down; malignant breast neoplasm; programs; public health relevance; response; transcription factor; transcriptome sequencing; tumor

DESCRIPTION (provided by applicant): Breast cancer is the most common cancer in women in the Western world, and is the leading cause of cancer related deaths in women worldwide. Many of the molecular factors known to be involved in breast cancer ultimately elicit their effects by causing changes in gene expression. A critical control point for regulating gene expression is at the level of mRNA transcription. In order to control the unchecked growth and invasiveness of breast cancer tumors, an understanding of disease-related perturbations in the transcription levels of genes critical to the progression of the disease must be obtained. The transcriptional activators NFATc2 and cJun have each individually been shown to activate transcription of genes that increase breast cancer cell invasiveness. Whether NFATc2 and cJun cooperate to activate transcription in breast cancer cells is not known, although their cooperation in controlling transcriptional programs in other biological systems is well-established. The intracellular localization of NFATc2 is controlled by levels of cytosolic calcium. Several chemical carcinogens are known to increase cytosolic calcium in mammary epithelial cells or breast cancer cells. Whether these chemicals cause NFATc2 to localize to the nucleus is not known. This pilot study will address the hypothesis that NFATc2 and cJun cooperate to activate transcription of genes that promote breast cancer invasiveness in response to environmental carcinogens known to increase cytosolic calcium. The proposal has three highly focused Specific Aims. 1) Determine the effect of environmental carcinogens known to increase cytosolic calcium on NFATc2 nuclear localization through the use of immunofluorescence. 2) Identify genes at which NFATc2 and cJun co-localize using ChIP-seq after treatment of mammary epithelial cells or breast cancer cells with a carcinogen. 3) Determine whether NFATc2 and cJun cooperate to upregulate expression of genes important to cell growth and invasiveness upon treatment with a carcinogen by knocking down the transcriptional activators and determining the effect on mRNA levels of select genes. The proposed research will determine whether NFATc2 and cJun cooperate to activate transcription in response to treating cells with a chemical carcinogen. Although the studies are focused on breast cancer because of the clear evidence that NFATc2 and cJun promote invasiveness of breast cancer cells, the research will also influence studies of other cancer types in which these factors are also thought to work. The results of these pilot studies will be used as a foundation for new lines of research using cell-based and biochemical studies to unravel the mechanisms by which NFATc2 and cJun activate transcription in breast cancer.

描述（由申请人提供）：乳腺癌是西方世界女性中最常见的癌症，也是全球女性癌症相关死亡的主要原因。许多已知的与乳腺癌有关的分子因素最终引发了它们的影响