INT-5/AROMATASE--EFFECT OF BREAST ESTROGEN IN NEOPLASIA
INT-5/芳香酶——乳腺雌激素对肿瘤的影响
基本信息
- 批准号:6346904
- 负责人:
- 金额:$ 1.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-07-15 至 2001-06-30
- 项目状态:已结题
- 来源:
- 关键词:apoptosis aromatase brca gene breast neoplasms cell proliferation cell transformation chemoprevention chorionic gonadotropin epidermal growth factor estrogen inhibitor estrogens genetic models genetic regulation genetically modified animals hormone regulation /control mechanism hormone related neoplasm /cancer insulinlike growth factor laboratory mouse neoplasm /cancer genetics oxidoreductase inhibitor preneoplastic state protooncogene retinoids telomerase transforming growth factors
项目摘要
We recently showed that the cellular gene at the mouse mammary
tumor virus integration site in the int-5 locus is identical to the gene
encoding aromatase (referred as int-5/aromatase). Aromatase
catalyzes the conversion of androgens to estrogens. Aromatase
levels are higher in breast tumors compared to normal tissue,
indicating that the in situ aromatase/breast estrogen may play a role
in breast cancer. No studies have demonstrated to direct
involvement of mammary aromatasein mammary tumorigenesis.
We have developed the int-5/aromaatase transgenic mice model,
and demonstrated for the first time that increased mammary
estrogenic activity due to the overexpression of int-5/aromatase in
female mammary glands leads to the induction of various
preneoplastic and neoplastic changes that are similar to early breast
cancer, that may, in turn, increase the risk of developing aggressive
breast cancer. In male transgenic mice, overexpression of int-
t/aromatase leads to increased mammary growth and hyperplastic
and dysplastic changes that are similar to gynecomastia (early male
breast cancer). These observations indicate that increased mammary
estrogen alone without the influence of circulating estrogen may be
sufficient to induce early breast cancer. Using int-5/aromatase in
vivo model we will: 1) examine the effect of increased mammary
estrogen on the regulation of oncogenes, growth factors, and tumor
suppressor genes implicated in breast cancer as will as genes
involved in programmed cell death; 2) determine whether the
synergistic interaction of estrogen (int-5/aromatase overexpression)
with c-myc or TGFalpha or p53 (plus/minus, minus/minus) in
transgenic crosses results in the acceleration and/or increase in the
incidence of breast cancer, 3) investigate whether exposing int-
5/aromatase transgenic animals to carcinogens leads to an
acceleration and/or increase in the incidence of breast cancer, and
4) determine whether blocking mammary estrogenic activity by
therapeutic interventions in early stages of mammary development
results in the prevention of preneoplastic/neoplastic changes that
may, in turn, reduce the occurrence of breast cancer. The outcome
of this study will help to understand the direct role of breast
estrogen in the initiation and/or promotion of breast cancer,
increased susceptibility to environmental carcinogens and may aid
in designing therapeutic approaches for the prevention of estrogen-
mediated breast cancer.
我们最近发现,小鼠乳腺癌细胞基因
int-5基因座中的肿瘤病毒整合位点与基因
编码芳香酶(称为int-5/芳香酶)。 芳香酶
催化雄激素转化为雌激素。 芳香酶
与正常组织相比,乳腺肿瘤中的水平较高,
这表明原位芳香化酶/乳腺雌激素可能在乳腺癌的发病中起作用,
在乳腺癌中。 没有研究表明,
乳腺芳香化酶参与乳腺肿瘤发生
我们建立了int-5/aromaatase转基因小鼠模型,
并首次证明了乳腺癌的发病率
由于int-5/芳香化酶的过度表达而引起的雌激素活性,
女性乳腺导致各种诱导
与早期乳腺癌相似的癌前和肿瘤变化
癌症,这可能会反过来增加发展侵略性的风险,
乳腺癌在雄性转基因小鼠中,
t/芳香化酶导致乳腺生长和增生增加
和发育异常的变化,类似于男性乳房发育(早期男性
乳腺癌)。这些观察结果表明,增加乳腺癌
没有循环雌激素的影响,
足以诱发早期乳腺癌。 使用int-5/芳香化酶
体内模型,我们将:1)检查增加乳腺癌的作用,
雌激素对癌基因、生长因子和肿瘤的调节
与乳腺癌有关的抑制基因,
参与程序性细胞死亡; 2)确定
雌激素协同作用(int-5/芳香化酶过表达)
与c-myc或TGF α或p53(加/减,减/减)在
转基因杂交导致了细胞增殖的加速和/或增加,
乳腺癌的发病率,3)调查是否暴露在
5/芳香化酶转基因动物致癌物导致
加速和/或增加乳腺癌的发病率,和
4)确定是否阻断乳腺雌激素活性,
乳腺发育早期阶段的治疗干预
导致预防肿瘤前/肿瘤变化,
可能反过来减少乳腺癌的发生。 成果
这项研究将有助于了解乳房的直接作用,
雌激素在引发和/或促进乳腺癌中的作用,
增加对环境致癌物的敏感性,
在设计预防雌激素的治疗方法时,
介导的乳腺癌。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)
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RAJESHWAR R TEKMAL其他文献
RAJESHWAR R TEKMAL的其他文献
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{{ truncateString('RAJESHWAR R TEKMAL', 18)}}的其他基金
CSF-1 and c-fms and the Early Endometriotic Lesion
CSF-1和c-fms与早期子宫内膜异位病变
- 批准号:
7755047 - 财政年份:2008
- 资助金额:
$ 1.53万 - 项目类别:
CSF-1 and c-fms and the Early Endometriotic Lesion
CSF-1和c-fms与早期子宫内膜异位病变
- 批准号:
7381269 - 财政年份:2008
- 资助金额:
$ 1.53万 - 项目类别:
CSF-1 and c-fms and the Early Endometriotic Lesion
CSF-1和c-fms与早期子宫内膜异位病变
- 批准号:
7569289 - 财政年份:2008
- 资助金额:
$ 1.53万 - 项目类别:
ROLE OF CSF1 AND ITS RECEPTOR IN ENDOMETRIOSIS
CSF1 及其受体在子宫内膜异位症中的作用
- 批准号:
6564753 - 财政年份:2001
- 资助金额:
$ 1.53万 - 项目类别:
ROLE OF CSF1 AND ITS RECEPTOR IN ENDOMETRIOSIS
CSF1 及其受体在子宫内膜异位症中的作用
- 批准号:
6417681 - 财政年份:2000
- 资助金额:
$ 1.53万 - 项目类别:
ROLE OF CSF1 AND ITS RECEPTOR IN ENDOMETRIOSIS
CSF1 及其受体在子宫内膜异位症中的作用
- 批准号:
6217868 - 财政年份:1999
- 资助金额:
$ 1.53万 - 项目类别:
ROLE OF CSF1 AND ITS RECEPTOR IN ENDOMETRIOSIS
CSF1 及其受体在子宫内膜异位症中的作用
- 批准号:
6302038 - 财政年份:1999
- 资助金额:
$ 1.53万 - 项目类别:
ROLE OF CSF1 AND ITS RECEPTOR IN ENDOMETRIOSIS
CSF1 及其受体在子宫内膜异位症中的作用
- 批准号:
6108856 - 财政年份:1998
- 资助金额:
$ 1.53万 - 项目类别:
Int5/Aromatase Effect of Breast Estrogen in Neoplasia
Int5/芳香酶对乳腺雌激素对肿瘤形成的影响
- 批准号:
6513098 - 财政年份:1997
- 资助金额:
$ 1.53万 - 项目类别:
INT-5/AROMATASE--EFFECT OF BREAST ESTROGEN IN NEOPLASIA
INT-5/芳香酶——乳腺雌激素对肿瘤的影响
- 批准号:
2733365 - 财政年份:1997
- 资助金额:
$ 1.53万 - 项目类别:
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