IDENTIFICATION OF ERES IN THE AMPHIREGULIN GENE
双调蛋白基因中 ERES 的鉴定
基本信息
- 批准号:2895889
- 负责人:
- 金额:$ 11.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-05-01 至 2000-04-30
- 项目状态:已结题
- 来源:
- 关键词:MCF7 cell breast neoplasms chloramphenicol acetyltransferase epidermal growth factor estradiol estrogen receptors genetic promoter element genetic regulatory element genetic transcription growth factor receptors hormone regulation /control mechanism hormone related neoplasm /cancer mammary epithelium messenger RNA molecular cloning neoplastic growth nuclear runoff assay receptor expression tissue /cell culture transfection transforming growth factors
项目摘要
DESCRIPTION (Applicant's Description):
The main goal of the applicant during this award period is to develop the
skills and the ability to become a productive, independent investigator able
to obtain continuous funding to support her own research program. She
anticipates that the research foundation she will develop in Dr. Maihle's
laboratory will result in future collaborative interactions as well. These
skills will be developed through the participation in: hands-on workshops
in molecular biology techniques, journal clubs, seminars, scientific
meetings, and through the interaction with other scientists in the field.
The Tumor Biology Program at the Mayo Clinic, MN provides her with an
outstanding academic environment to accomplish this goal. The proposed
research study will provide her the opportunity to master the commonly used
research approaches in tumor biology. Breast carcinoma, one of the most
common cancers in women, may have both its genesis and growth influence by
hormonal factors. Patient's hormonal environment has been shown to affect
the clinical course of breast cancer. The effect of estrogen in the
stimulation of cell growth in breast cancer cell lines depends on the
presence of active functional estrogen receptors. Moreover, the loss of
estrogen receptor responsiveness is associated with hormone growth
independence in breast cancer cell lines, and with malignant progression and
poor prognosis. The mechanism of estrogen action in growth stimulation is
poorly understood. However, it has been postulated that estrogen may act,
at least in part, through the endogenous production of growth factors that
may function in an autocrine/paracrine or juxtacrine manner. In Dr.
Maihle's laboratory, it has been demonstrated that one GF/GFR circuit is
regulated by both estrogen and androgen, i.e., the a m phiregulin/epidermal
growth factor receptor pathway (AR/EGFR). The synthesis of these gene
products has been shown to be regulated at both mRNA and protein levels.
Dr. Maihle and others have shown that regulation of the EGFR synthesis
occurs at the transcriptional level. In addition, it has been r e p orted
that estrogen stimulates the induction of AR mRNA at the transcriptional
level in estrogen responsive cells. In this application the applicants
propose to test the hypothesis that the mechanism of AR induction by steroid
hormones occurs at the transcriptional level and that the action of steroids
in the regulation of breast carcinoma cell growth is through the AR/EGFR
pathway. To test this hypothesis they propose to determine the kinetics of
induction of EGFR, AR, and TGF-alpha mRNAs by estrogen in breast carcinoma
cells and to identify and characterize the estrogen response elements in the
AR gene.
描述(申请人描述):
申请人在此期间的主要目标是开发
技能和能力,成为一个富有成效的,独立的调查员,
以获得持续的资金来支持她自己的研究计划。 她
预计她将在Maihle博士的研究基础上发展
实验室将导致未来的合作互动,以及。 这些
将通过参加以下活动发展技能:
在分子生物学技术,期刊俱乐部,研讨会,科学
会议,并通过与该领域的其他科学家的互动。
明尼苏达州马约诊所的肿瘤生物学项目为她提供了一个
良好的学术环境,以实现这一目标。 拟议
研究性学习将使她有机会掌握常用的
肿瘤生物学的研究方法。 乳腺癌,最常见的癌症之一
常见的女性癌症,可能有其起源和生长的影响,
荷尔蒙因素 病人的荷尔蒙环境会影响
乳腺癌的临床过程。 雌激素在乳腺癌中的作用
乳腺癌细胞系中细胞生长的刺激取决于
活性功能性雌激素受体的存在。 此外,损失
雌激素受体反应性与激素生长有关
在乳腺癌细胞系中的独立性,以及恶性进展和
预后不良。 雌激素在生长刺激中的作用机制是
不太了解。 然而,据推测雌激素可能起作用,
至少部分是通过内源性生长因子的产生,
可能以自分泌/旁分泌或外分泌方式起作用。 博士米切尔
Maihle的实验室,已经证明,一个GF/GFR电路是
由雌激素和雄激素调节,即,调蛋白/表皮
生长因子受体途径(AR/EGFR)。 这些基因的合成
已经证明,在mRNA和蛋白质水平上都可以调节蛋白质产物。
博士Maihle和其他人已经表明,EGFR合成的调节
发生在转录水平。 此外,它已被重新分配,
雌激素刺激AR mRNA在转录水平的诱导,
雌激素反应细胞的水平。 在本申请中,申请人
建议检验类固醇诱导AR的机制
激素的作用发生在转录水平上,
在乳腺癌细胞生长的调控中是通过AR/EGFR
通路 为了验证这一假设,他们建议确定
雌激素对乳腺癌EGFR、AR和TGF-α mRNA诱导作用
细胞中的雌激素反应元件,并确定和表征雌激素反应元件中,
AR基因。
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)
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{{ truncateString('ELSA M CORA', 18)}}的其他基金
IDENTIFICATION OF ERES IN THE AMPHIREGULIN GENE
双调蛋白基因中 ERES 的鉴定
- 批准号:
2616911 - 财政年份:1998
- 资助金额:
$ 11.04万 - 项目类别:
IDENTIFICATION OF ERES IN THE AMPHIREGULIN GENE
双调蛋白基因中 ERES 的鉴定
- 批准号:
6173372 - 财政年份:1998
- 资助金额:
$ 11.04万 - 项目类别:
IDENTIFICATION OF ERES IN THE AMPHIREGULIN GENE
双调蛋白基因中 ERES 的鉴定
- 批准号:
6376375 - 财政年份:1998
- 资助金额:
$ 11.04万 - 项目类别:
IDENTIFICATION OF ERES IN THE AMPHIREGULIN GENE
双调蛋白基因中 ERES 的鉴定
- 批准号:
6594191 - 财政年份:1998
- 资助金额:
$ 11.04万 - 项目类别:
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