Blockade of cMYC oncogenic function by pregnancy-induced alterations and remodeling of the mammary gland
通过妊娠引起的乳腺改变和重塑来阻断 cMYC 致癌功能
基本信息
- 批准号:10734182
- 负责人:
- 金额:$ 51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectAgeBRCA1 geneBiochemicalBirthBreastBreast AdenocarcinomaBreast Cancer Risk FactorBreast Epithelial CellsCancer ModelCellsCellular biologyChromatinDNA MethylationDataDevelopmentEZH2 geneEnhancersEpigenetic ProcessEventExposure toFemaleFutureGene ExpressionGenetic TranscriptionGoalsHormonesHumanHyperplasiaIncidenceKnowledgeLesionLifeLinkMachine LearningMalignant - descriptorMalignant NeoplasmsMammary TumorigenesisMammary glandMediatingMethodsModelingMolecularMorphogenesisMusNulliparityOncogenesOncogenicOrganoidsOutcomeOutputPathway interactionsPhenotypePhysiologyPregnancyPreventive treatmentPropertyRegulatory ElementReproductionResearchRiskRodentRodent ModelRoleSystemTestingTherapeutic InterventionTissuesTranscriptional ActivationTranscriptional RegulationTransgenic AnimalsTransgenic MiceWild Type MouseWomanWorkc-myc Genescancer subtypescell typechromatin remodelingcofactorepidemiology studyepigenomeepigenomicsgenetic approachin vivoinsightmalignant breast neoplasmmammarymouse modelnoveloverexpressionparouspost pregnancypregnantprepregnancypreventprotective effectresponsesmall molecule inhibitortumortumorigenesis
项目摘要
Abstract/Project Summary
The goal of this proposal is to understand how transitions through pregnancy influence the molecular and cellular
state of mammary epithelial cells and oncogenesis. Numerous epidemiological studies have found that
pregnancy alters the risk of breast cancer. These studies have shown consistently that a full-term pregnancy
prior to the age of 25 is associated with a one-third decrease in the life-time incidence of breast cancer. While a
protective effect of pregnancy has been validated in rodent models of cancer, the underlying molecular basis for
this effect remains unclear.
We have found that pregnancy leads to persistent changes in the epigenome and enhancer landscape of MECs.
Using an inducible c-MYC mouse model, we also find that oncogenesis and the transcriptional output
downstream of this oncogene are reduced in post-pregnancy MECs. In this proposal we will investigate the
molecular basis underlying these robust phenotypes. We will use epigenomics, ex vivo, in vivo and biochemical
methods to define how the transcriptional function of c-MYC is modulated by pregnancy. We hypothesize that c-
MYC interactions with cofactors and with specific cis-regulatory elements are altered in this system.
We will also study how specific chromatin regulators contribute to pregnancy-mediated epigenomic rewiring.
These efforts will build upon our recent data suggesting that EZH2 supports the post-pregnancy epigenome in
wild-type mice. Collectively, this research will provide fundamental insights into the cell biology of the mammary
gland and carry the potential for discoveries that could be harnessed to develop preventative treatments that
modulate breast cancer risk in humans.
摘要/项目摘要
这项建议的目标是了解如何通过怀孕的过渡影响分子和细胞的
乳腺上皮细胞的状态和肿瘤发生。许多流行病学研究发现,
怀孕会改变患乳腺癌的风险。这些研究一致表明,足月妊娠
在25岁之前,与乳腺癌终生发病率下降三分之一有关。而
妊娠的保护作用已在啮齿动物癌症模型中得到验证,这是妊娠的潜在分子基础。
这一影响尚不清楚。
我们已经发现,怀孕导致MEC的表观基因组和增强子景观的持续变化。
使用可诱导的c-MYC小鼠模型,我们还发现肿瘤发生和转录输出
在妊娠后MEC中,该癌基因下游的表达减少。在本提案中,我们将调查
这些强大的表型背后的分子基础。我们将使用表观基因组学,体外,体内和生化
方法来确定如何通过怀孕调节c-MYC的转录功能。我们假设-
MYC与辅因子和特定顺式调控元件的相互作用在该系统中被改变。
我们还将研究特定的染色质调节因子如何促进妊娠介导的表观基因组重连。
这些努力将建立在我们最近的数据上,这些数据表明EZH 2支持妊娠后表观基因组,
野生型小鼠。总的来说,这项研究将为乳腺癌的细胞生物学提供基本的见解。
腺和携带的发现,可以利用开发预防性治疗,
调节人类乳腺癌风险。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Camila dos Santos其他文献
Camila dos Santos的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Camila dos Santos', 18)}}的其他基金
Defining the cellular and molecular effects of aging and age of pregnancy on breast tissue homeostasis and cancer initiation
定义衰老和怀孕年龄对乳腺组织稳态和癌症发生的细胞和分子影响
- 批准号:
10264871 - 财政年份:2020
- 资助金额:
$ 51万 - 项目类别:
Defining the cellular and molecular effects of aging and age of pregnancy on breast tissue homeostasis and cancer initiation
定义衰老和怀孕年龄对乳腺组织稳态和癌症发生的细胞和分子影响
- 批准号:
10656192 - 财政年份:2020
- 资助金额:
$ 51万 - 项目类别:
Defining the cellular and molecular effects of aging and age of pregnancy on breast tissue homeostasis and cancer initiation
定义衰老和怀孕年龄对乳腺组织稳态和癌症发生的细胞和分子影响
- 批准号:
10417248 - 财政年份:2020
- 资助金额:
$ 51万 - 项目类别:
Probing the role of epigenomics in Brca1-deficient mammary tumors.
探讨表观基因组学在 Brca1 缺陷型乳腺肿瘤中的作用。
- 批准号:
10580724 - 财政年份:2020
- 资助金额:
$ 51万 - 项目类别:
Probing the role of epigenomics in Brca1-deficient mammary tumors.
探讨表观基因组学在 Brca1 缺陷型乳腺肿瘤中的作用。
- 批准号:
10331847 - 财政年份:2020
- 资助金额:
$ 51万 - 项目类别:
Defining the cellular and molecular effects of aging and age of pregnancy on breast tissue homeostasis and cancer initiation
定义衰老和怀孕年龄对乳腺组织稳态和癌症发生的细胞和分子影响
- 批准号:
10090965 - 财政年份:2020
- 资助金额:
$ 51万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 51万 - 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
- 批准号:
2601817 - 财政年份:2021
- 资助金额:
$ 51万 - 项目类别:
Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
- 批准号:
2029039 - 财政年份:2020
- 资助金额:
$ 51万 - 项目类别:
Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
- 批准号:
9888417 - 财政年份:2019
- 资助金额:
$ 51万 - 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
- 批准号:
17K11318 - 财政年份:2017
- 资助金额:
$ 51万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 51万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 51万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 51万 - 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
- 批准号:
BB/M50306X/1 - 财政年份:2014
- 资助金额:
$ 51万 - 项目类别:
Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
- 批准号:
288272 - 财政年份:2013
- 资助金额:
$ 51万 - 项目类别:
Miscellaneous Programs