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Novel Gene Networks in Breast Development and Cancer

乳房发育和癌症中的新基因网络

基本信息

批准号：
7919121
负责人：
Steffi Oesterreich
金额：
$ 17.65万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7919121
关键词：
Novel Gene Networks Breast Development

项目摘要

DESCRIPTION (provided by applicant): Gene networks controlling the complex, hormonally-regulated growth and development of the mammary gland are likely to involve the same genes which, aberrantly expressed, contribute to the onset of breast cancer and its progression to metastasis. The overall goal of this Program Project is thus to identify and characterize these gene pathways, in order to define inclusive expression patterns that accurately predict the likelihood of clinical recurrence so that patients can be selected to receive or be spared adjuvant therapy. Several novel gene networks which we have found to have roles in normal mammary development and progression to cancer will be explored in terms of their interactions and their potential as targets for treatment and prevention, and we will seek to integrate comprehensive gene amplification and expression information combining two molecular profiling approaches. The individual projects are: 1) integrating RNA expression and array CGH profiles to predict long-term breast cancer progression, using a unique collection of frozen tumor specimens with >12 years clinical follow-up to identify individual gene pathways and comprehensive molecular signatures indicating the metastatic capability of an individual patient's tumor; 2) defining the tumor suppressor role of the SAFB scaffold attachment factors, whose genetic locus we have found to show the highest loss of heterozygosity yet reported in breast cancer; 3) targeting IGF-I and its cross-talk with the estrogen pathway in progression to malignancy, based on our findings and others that activation of IGF system components is prognostically ominous, that serum IGF-I is a breast cancer risk factor, and that there is direct positive feedback between the IGF and estrogen systems; 4) determining the role of the Ptc1 hedgehog receptor in mammary ductal development and progression to neoplasia, since we find that aberrant Ptc1 leads to ductal hyperplasia and that the hedgehog network regulates functions likely to be critical for metastatic behavior; 5) investigate the role of p190-B RhoGAP interactions in mammary development, particularly the invasive growth of the terminal end bud into the mammary fat pad, and also in breast cancer invasion and metastasis. These Projects will be supported by a Pathology and Tissue Resource, a Biostatistics and Array Analysis Core, and Animal Handling and Imaging Core. These highly interactive projects are designed to enhance our knowledge of how mammary development can become malignant and invasive, and to define gene amplification and expression profiles which will select those breast cancer patients who may truly benefit from adjuvant therapy.

描述（由申请人提供）：控制乳腺复杂的、激素调节的生长和发育的基因网络可能涉及相同的基因，这些基因的异常表达导致乳腺癌的发病及其进展为转移。因此，该计划项目的总体目标是识别和表征这些基因途径，以便定义准确预测临床复发可能性的包容性表达模式，以便选择患者接受或不接受辅助治疗。我们发现的几个在正常乳腺发育和癌症进展中发挥作用的新基因网络将根据它们的相互作用及其作为治疗和预防目标的潜力进行探索，我们将寻求结合两种分子分析方法来整合全面的基因扩增和表达信息。各个项目包括：1) 整合 RNA 表达和阵列 CGH 谱来预测长期乳腺癌进展，使用独特的冷冻肿瘤标本集合和超过 12 年的临床随访来识别个体基因通路和综合分子特征，表明个体患者肿瘤的转移能力； 2）定义SAFB支架附着因子的肿瘤抑制作用，我们发现其遗传位点在乳腺癌中表现出最高的杂合性损失； 3）针对IGF-I及其与雌激素途径在恶性肿瘤进展过程中的相互作用，根据我们和其他人的研究结果，IGF系统成分的激活在预后上是不祥的，血清IGF-I是乳腺癌的危险因素，并且IGF和雌激素系统之间存在直接的正反馈； 4）确定Ptc1刺猬受体在乳腺导管发育和肿瘤进展中的作用，因为我们发现异常的Ptc1导致导管增生，并且刺猬网络调节可能对转移行为至关重要的功能； 5) 研究p190-B RhoGAP相互作用在乳腺发育中的作用，特别是终芽侵入乳腺脂肪垫的生长，以及在乳腺癌侵袭和转移中的作用。这些项目将得到病理学和组织资源、生物统计学和阵列分析核心以及动物处理和成像核心的支持。这些高度互动的项目旨在增强我们对乳腺发育如何变得恶性和侵袭性的了解，并定义基因扩增和表达谱，从而选择那些可能真正从辅助治疗中受益的乳腺癌患者。

项目成果

期刊论文数量（164）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Relationship of clone 4 estrogen receptor variant messenger RNA expression to some known prognostic variables in human breast cancer.

DOI：
发表时间：
1995-02
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
0
作者：
L. Murphy;S. Hilsenbeck;Helmut Dotzlaw;S. Fuqua
通讯作者：
L. Murphy;S. Hilsenbeck;Helmut Dotzlaw;S. Fuqua

Prognostic factors in axillary node-negative breast cancer.

腋窝淋巴结阴性乳腺癌的预后因素。