Role of Estrogen and Iron in Breast Cancer
雌激素和铁在乳腺癌中的作用
基本信息
- 批准号:7193116
- 负责人:
- 金额:$ 16.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-05 至 2009-06-30
- 项目状态:已结题
- 来源:
- 关键词:17p8-Oxo-2&apos-DeoxyguanosineAntigensBreast Cancer Risk FactorCancer EtiologyCancer cell lineCell LineCellsCharacteristicsConditionDNADeoxyguanosineDevelopmentEpithelialEstradiolEstrogen ReceptorsEstrogensFatty acid glycerol estersFemaleGene MutationGenesGrowthHealth BenefitHemochromatosisHemorrhageImplantIncidenceIronMammary Gland ParenchymaMammary NeoplasmsMammary glandMeasuresMediatingMenopauseMethodsModelingMouse StrainsMusMutationOvariectomyPlayPostmenopausePremenopauseProgesterone ReceptorsProteinsPubertyRNARateResearchRisk FactorsRoleSerum iron level resultSmall Interfering RNATestingTransfer RNATransferrin ReceptorTransgenic OrganismsTumor VolumeTumorigenicityWeekWild Type MouseWomanWomen&aposs Healthcancer cellimplantationmalignant breast neoplasmmouse modelmutantneoplasticreceptortumortumor growthuptakeyoung adult
项目摘要
DESCRIPTION (provided by applicant): Breast cancer (BC) incidence rates are much higher in post- than pre-menopausal women. Estrogen is a well-known risk factor for BC development. Yet, total estrogen levels are lower in post- than pre-menopausal women. This apparent discrepancy calls for new research to better understand BC etiology and mechanisms. In the present study, we hypothesize that an accumulation of high iron levels due to menopause is one of the pre-neoplastic changes in post-menopausal women, and in the presence of high local estrogen in the breast tissue, both iron and estrogen greatly promote breast tumor growth and oxidative damage. We will test this hypothesis using an ovariectomized (OVX) transgenic iron-loaded mouse model carrying hemochromatosis (HFE) gene mutation. This model has a decreased estrogen level because of the OVX, but an increased iron level due to the HFE gene mutation, thus mimicking post-menopausal conditions. In Aim1, we will assess the role of estrogen in mammary epithelial proliferation and spontaneous tumor formation in wild-type and iron loaded HFE+/- mice. Female wild-type C57BL6 mice and HFE+/- mice will undergo OVX. After implantation of 17beta-estradiol (E2), Ki-67, a proliferation-specific antigen, and spontaneous tumor incidence of the iron-loaded mutant and wild-type mice will be compared. In Aim 2, we will assess whether E2 induces a higher tumor take and growth of mammary cancer in HFE+/- mice than in wild-type mice. MXT+ mammary cancer cells will be inoculated into the mammary fat pads of wild-type and HFE+/- mice. Mammary cancer tumorigenicity and tumor latency as well as tumor volume will be measured. Levels of oxidative DNA and protein in breast tissues will be determined and compared. In Aim 3, we will determine whether E2-mediated tumor growth is iron-dependent. The MXT+ cell line will be transfected with small interfering RNA (siRNA) of transferring receptor. Mammary cancer will be measured and compared between the siRNA transfectants and the parental cells. We expect to show that iron plays an important role in estrogen-dependent BC and this new direction of research may greatly benefit the health of female baby- boomers.
描述(由申请人提供):绝经后女性的乳腺癌(BC)发病率比绝经前女性高得多。雌激素是乳腺癌发生的一个众所周知的危险因素。然而,绝经后女性的总雌激素水平低于绝经前女性。这种明显的差异需要新的研究来更好地了解 BC 的病因和机制。在本研究中,我们假设,由于更年期导致的高铁水平积累是绝经后女性的肿瘤前变化之一,并且在乳腺组织中存在高局部雌激素的情况下,铁和雌激素都会极大地促进乳腺肿瘤的生长和氧化损伤。我们将使用携带血色素沉着症(HFE)基因突变的卵巢切除(OVX)转基因铁负载小鼠模型来检验这一假设。该模型由于 OVX 而雌激素水平降低,但由于 HFE 基因突变而铁水平升高,从而模拟绝经后状况。在 Aim1 中,我们将评估雌激素在野生型和铁负载 HFE+/- 小鼠乳腺上皮增殖和自发肿瘤形成中的作用。雌性野生型 C57BL6 小鼠和 HFE+/- 小鼠将接受 OVX。植入17β-雌二醇(E2)后,将比较载铁突变型小鼠和野生型小鼠的增殖特异性抗原Ki-67以及自发性肿瘤发生率。在目标 2 中,我们将评估 E2 是否会诱导 HFE+/- 小鼠比野生型小鼠更高的肿瘤发生率和乳腺癌生长。 MXT+乳腺癌细胞将被接种到野生型和HFE+/-小鼠的乳腺脂肪垫中。将测量乳腺癌的致瘤性、肿瘤潜伏期以及肿瘤体积。将测定并比较乳腺组织中氧化 DNA 和蛋白质的水平。在目标 3 中,我们将确定 E2 介导的肿瘤生长是否依赖于铁。 MXT+细胞系将用转移受体的小干扰RNA (siRNA)转染。将测量并比较 siRNA 转染子和亲本细胞的乳腺癌情况。我们希望证明铁在雌激素依赖性乳腺癌中发挥着重要作用,这一新的研究方向可能会极大地有益于婴儿潮一代女性的健康。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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利用方解石降低煤矿粉尘毒性
- 批准号:
7863384 - 财政年份:2009
- 资助金额:
$ 16.9万 - 项目类别:
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- 批准号:
7725070 - 财政年份:2008
- 资助金额:
$ 16.9万 - 项目类别:
EFFICIENT ALGORITHMS FOR PROTEIN TERTIARY STRUCTURE PREDICTION
蛋白质三级结构预测的高效算法
- 批准号:
7610018 - 财政年份:2007
- 资助金额:
$ 16.9万 - 项目类别:
IRON, CALCIUM AND OXIDATIVE STRESS IN LUNG INJURY
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6042278 - 财政年份:1999
- 资助金额:
$ 16.9万 - 项目类别:
IRON, CALCIUM AND OXIDATIVE STRESS IN LUNG INJURY
肺损伤中的铁、钙和氧化应激
- 批准号:
6335451 - 财政年份:1999
- 资助金额:
$ 16.9万 - 项目类别:
IRON, CALCIUM AND OXIDATIVE STRESS IN LUNG INJURY
肺损伤中的铁、钙和氧化应激
- 批准号:
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- 资助金额:
$ 16.9万 - 项目类别: