Role of Nmi in retarding breast tumor growth.

Nmi 在延缓乳腺肿瘤生长中的作用。

基本信息

  • 批准号:
    8206858
  • 负责人:
  • 金额:
    $ 26.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-03-04 至 2012-11-30
  • 项目状态:
    已结题

项目摘要

Research in our laboratory focuses on understanding the role of N-Myc interactor (Nmi) in cancer biology [1]. Our interest in this molecule was triggered when we saw that its expression was diminished in aggressive breast cancer cell lines. Interestingly though, Nmi expression could be induced in these cells using interferon-¿ (IFN-¿) [1]. We found that the induced mRNA had a wild type sequence, implying that the induced Nmi protein was capable of its normal biological activities. To test its functional role, we constitutively expressed Nmi in the human breast cancer cell line, MDA-MB- 231. Functional studies of the expressors showed that Nmi reduced the ability of tumor cells to invade and grow under anchorage independent conditions. Xenograft studies in nude mice showed that Nmi expressors had reduced tumor growth in vivo [1]. Further analysis of these expressors revealed that Dickkopf-1 (Dkk1), a soluble inhibitor of the Wnt/¿- catenin signaling pathway, was significantly upregulated in the Nmi expressing clones concurrent with reduced levels of the critical transcription co-factor of Wnt pathway, ¿-catenin. Dkk1 has been reported to suppress primary tumor growth rates in several studies involving breast cancer [2, 3] and is a factor implicated in the anti-tumor effects elicited by IFN-¿ [4]. Wnt/¿-catenin signaling is important in development as well as cell proliferation. While previously shown to be a critical player in colon cancer progression, the role of Wnt/¿-catenin signaling in breast cancer is not clearly defined [5]. The overall objective of this proposed work is to understand the regulation of Wnt/¿-catenin signaling by Nmi and to determine the role of this pathway in suppression of breast tumor growth. HYPOTHESIS Inhibition of the Wnt/¿-catenin signaling pathway by upregulation of Dkk1 is critical to the role of Nmi in reducing tumor growth. Aim 1: To test the hypothesis that knockdown of Nmi expression will activate the Wnt/¿-catenin signaling. Aim 2: To determine the mechanism of regulation of Dkk1 and ¿-catenin by Nmi. Aim 3: To evaluate the role of Dkk1 in mediating the retardation of tumor growth by Nmi. Aim 4: To determine correlation between loss of Nmi expression and activated Wnt/¿-catenin signaling in patient derived breast cancer specimens.
我们实验室的研究重点是了解N-Myc相互作用(Nmi)在癌症中的作用

项目成果

期刊论文数量(0)
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Rajeev S Samant其他文献

Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-κB activation
  • DOI:
    10.1186/1476-4598-6-6
  • 发表时间:
    2007-01-16
  • 期刊:
  • 影响因子:
    33.900
  • 作者:
    Rajeev S Samant;David W Clark;Rebecca A Fillmore;Muzaffer Cicek;Brandon J Metge;Kondethimmana H Chandramouli;Ann F Chambers;Graham Casey;Danny R Welch;Lalita A Shevde
  • 通讯作者:
    Lalita A Shevde

Rajeev S Samant的其他文献

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{{ truncateString('Rajeev S Samant', 18)}}的其他基金

A novel strategy to debilitate breast cancer metastasis
削弱乳腺癌转移的新策略
  • 批准号:
    10508990
  • 财政年份:
    2022
  • 资助金额:
    $ 26.9万
  • 项目类别:
Mechanisms that impact metastatic progression of triple negative breast cancer
影响三阴性乳腺癌转移进展的机制
  • 批准号:
    10009841
  • 财政年份:
    2017
  • 资助金额:
    $ 26.9万
  • 项目类别:
Mechanisms that impact metastatic progression of triple negative breast cancer
影响三阴性乳腺癌转移进展的机制
  • 批准号:
    10347166
  • 财政年份:
    2017
  • 资助金额:
    $ 26.9万
  • 项目类别:
Mechanisms that impact metastatic progression of triple negative breast cancer
影响三阴性乳腺癌转移进展的机制
  • 批准号:
    10554270
  • 财政年份:
    2017
  • 资助金额:
    $ 26.9万
  • 项目类别:
Dietary intervention of non-classical Wnt signaling
非经典 Wnt 信号传导的饮食干预
  • 批准号:
    9889045
  • 财政年份:
    2016
  • 资助金额:
    $ 26.9万
  • 项目类别:
Dietary intervention of non-classical Wnt signaling
非经典 Wnt 信号传导的饮食干预
  • 批准号:
    9240612
  • 财政年份:
    2016
  • 资助金额:
    $ 26.9万
  • 项目类别:
Role of Nmi in retarding breast tumor growth.
Nmi 在延缓乳腺肿瘤生长中的作用。
  • 批准号:
    7885957
  • 财政年份:
    2010
  • 资助金额:
    $ 26.9万
  • 项目类别:
Role of Nmi in retarding breast tumor growth.
Nmi 在延缓乳腺肿瘤生长中的作用。
  • 批准号:
    8038299
  • 财政年份:
    2010
  • 资助金额:
    $ 26.9万
  • 项目类别:
Role of Nmi in retarding breast tumor growth.
Nmi 在延缓乳腺肿瘤生长中的作用。
  • 批准号:
    8433522
  • 财政年份:
    2010
  • 资助金额:
    $ 26.9万
  • 项目类别:

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