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INDUCIBLE MOUSE MODELS FOR SKIN AND HEAD AND NECK CANCER

皮肤癌和头颈癌的诱导小鼠模型

基本信息

批准号：
7922334
负责人：
Dennis Roop
金额：
$ 21.4万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2010-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The overall objective of this project is the generation of inducible mouse models that closely mimic the development of human skin and head and neck cancers. My colleagues and I have recently developed inducible mouse models that allow the activation of oncogenes or inactivation of tumor suppressor genes in a restricted area of the skin, oral cavity or esophagus in stem cells that renew these stratified epithelia. Thus, we can create mice with discrete genetic changes in somatic cells that are identical to events that are thought to occur in human tumors. The genetic changes identified to date are primarily associated with early stages of tumor development. Much less is known about genetic changes that occur as tumors progress to metastatic lesions. Thus, our application will focus on recently discovered candidate genes implicated in promoting tumor progression through mechanisms that are both dependent on and independent of genomic instability. To identify novel genetic changes associated with tumor progression in our inducible mouse models, we will analyze tumors using both Affymetrix arrays and BAC/CGH arrays. In parallel studies, we will also analyze human skin and head and neck tumors which exhibit an aggressive nature and propensity to metastasize by Affymetrix arrays and BAC/CGH arrays and compare these findings with results obtained from analysis of the mouse tumors. Our inducible mouse models develop tumors as the result of discrete genetic changes, therefore these models are ideally suited to test novel drugs designed to interfere with specific gene products or signaling pathways. Pilot experiments will be performed to assess the utility of these models as tools for translational studies. Imaging will be utilized for the early detection of metastatic lesions in these studies and to monitor regression following treatment.

描述（由申请人提供）：该项目的总体目标是产生可诱导小鼠模型，以密切模拟人类皮肤癌和头颈癌的发展。我和我的同事最近开发了诱导型小鼠模型，允许在皮肤、口腔或食管的限制区域中，在更新这些分层上皮的干细胞中激活癌基因或失活肿瘤抑制基因。因此，我们可以创造出在体细胞中具有离散遗传变化的小鼠，这些变化与被认为发生在人类肿瘤中的事件相同。迄今为止发现的遗传变化主要与肿瘤发展的早期阶段有关。对于肿瘤发展到转移性病变时发生的遗传变化知之甚少。因此，我们的申请将集中在最近发现的候选基因参与促进肿瘤进展的机制，既依赖于和独立于基因组的不稳定性。为了在我们的诱导型小鼠模型中鉴定与肿瘤进展相关的新的遗传变化，我们将使用Affyssin阵列和BAC/CGH阵列分析肿瘤。在平行研究中，我们还将分析人类皮肤和头颈部肿瘤，这些肿瘤表现出侵袭性和转移倾向，通过Affyssin阵列和BAC/CGH阵列进行分析，并将这些发现与小鼠肿瘤分析结果进行比较。我们的诱导型小鼠模型由于离散的遗传变化而产生肿瘤，因此这些模型非常适合测试旨在干扰特定基因产物或信号通路的新型药物。将进行试点实验，以评估这些模型作为翻译研究的工具的效用。在这些研究中，成像将用于早期检测转移性病变，并监测治疗后的消退。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Timed NF-kappaB inhibition in skin reveals dual independent effects on development of HED/EDA and chronic inflammation.

DOI：
10.1038/jid.2009.126
发表时间：
2009-11
期刊：
The Journal of investigative dermatology
影响因子：
0
作者：
Maria H. Ulvmar;I. Sur;S. Mémet;R. Toftgård
通讯作者：
Maria H. Ulvmar;I. Sur;S. Mémet;R. Toftgård

Development of mammary tumors by conditional expression of GLI1.

DOI：
10.1158/0008-5472.can-08-3938
发表时间：
2009-06-01
期刊：
Cancer research
影响因子：
11.2
作者：
Fiaschi M;Rozell B;Bergström A;Toftgård R
通讯作者：
Toftgård R

Loss of Trp53 promotes medulloblastoma development but not skin tumorigenesis in Sufu heterozygous mutant mice.

DOI：
10.1002/mc.20852
发表时间：
2012-09
期刊：
MOLECULAR CARCINOGENESIS
影响因子：
4.6
作者：
Heby-Henricson, Karin;Bergstrom, Asa;Rozell, Bjorn;Toftgard, Rune;Teglund, Stephan
通讯作者：
Teglund, Stephan

Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia.

DOI：
10.1016/j.ydbio.2009.04.009
发表时间：
2009-06-15
期刊：
DEVELOPMENTAL BIOLOGY
影响因子：
2.7
作者：
Jia, Jinping;Kolterud, Asa;Zeng, Huiqing;Hoover, Amber;Teglund, Stephan;Toftgard, Rune;Liu, Aimin
通讯作者：
Liu, Aimin

Tumor suppressor gene co-operativity in compound Patched1 and suppressor of fused heterozygous mutant mice.