CHORIONIC GONADOTROPIN AND MAMMARY CARCINOGENESIS

绒毛膜促性腺激素与乳腺癌发生

基本信息

批准号：
2707470
负责人：
IRMA H. RUSSO
金额：
$ 7.21万
依托单位：
FOX CHASE CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-01-01 至 1999-12-31
项目状态：
已结题

项目摘要

Our studies of the pathogenesis an deprevention of mammary cancer led us to conclude that diffentiation is an effective and physiologic mechanism for preventing chemically induced mammary carcinogenesis, since the fully differentiated mammary gland of parous rats is refractory to the initiation of 7, 12-demethylbenz(a)anthracene (DMBA_-induced mammary carcinomas. The observations that this effect is mimicked by treatment of young virgin rats with the placental hormone chorionic gonadotropin (CG), which also prevent the progression of the tumors, making this model ideal for its utilization in human breast cancer prevention and therapy of the human disease. The finding that hCG induces in the mammary gland profuse lobular formalin and the expression of inhibin led us to postulate that the action of hCG might be mediated by this inhibitor growth factor which might act as a local regulatory factor. We will apply our experience on the pathogenesis of DMBA-induced mammary cancer for identifying intraductal proliferations (IDPs), in situ carcinomas and invasive carcinomas to test the effect of hCG on these lesin. We propose to clarify whether hCG inhibit tumorigenesis by inducing differentiation of the neoplastically initiated cells, whether it merely inhibits cell proliferation, or drives the cells to programmed cell death. In this setting, we will define differentiation by the ability of the neoplastically initiated cells to synthesize the milk protein beta casein and inhibin; cell proliferation will be measured by the ability of the cells to incorporate DNA precursors and the number of cells undergoing programmed cell death will be measured in the same tumors by determining the expression of transforming growth factor (TGF)beta1, by detection of the TRPM-2 gene and by measuring he apoptotic index. With this methodology, we propose to investigate the mechanism(s) by which hCG inhibits the progression of DMBA-induced rat mammary carcinomas by determining whether tumor growth is modulated by induction of cell differentiation, inhibition of cell proliferation and/or activation of programmed cell death. We also propose to determine whether the inhibitory effect of hCG on tumor progression is a direct effect of the hormone on tumor cells effected by the binding of hCG to a specific lutropin-choriogonadotropin receptor (LH-CG-R), whether this receptor is treatment or by hCG itself; and finally, we propose to determine what is the direct effect of inhibin on mammary tumors and whether it is the mediator of the differentiations effect of hCG on the mammary gland. The answer to these questions will help to determine whether hormonally induced differentiation is a plausible mechanism for developing more rationale bases for cancer prevention and therapy.

我们对发病机理的研究引发了我们得出结论，扩散是一种有效且生理的机制用于预防化学诱导的乳腺癌发生，因为释放大鼠的分化乳腺对 7、12-甲基苯子（A）蒽（DMBA_诱导的乳腺癌。观察到这种效果被治疗模仿年轻的维尔京老鼠，胎盘激素绒毛膜促性腺激素（CG），这也防止了肿瘤的进展，使该模型它用于预防人类乳腺癌和治疗的理想人类疾病。 HCG在乳腺中诱导的发现大量小叶福尔马林和抑制素的表达导致我们假设HCG的作用可能是由该抑制剂介导的生长因子可能充当局部调节因素。我们将应用我们在DMBA诱导的乳腺癌发病机理上的经验用于识别导管内增殖（IDP），原位癌和侵入性癌以测试HCG对这些Lesin的影响。我们建议澄清HCG是否通过诱导分化抑制肿瘤发生新塑料引发的细胞，是否仅抑制细胞增殖或将细胞驱动到编程的细胞死亡。在这个设置，我们将根据能力来定义差异化肿瘤引发的细胞合成牛奶蛋白β酪蛋白和抑制素；细胞增殖将通过细胞结合DNA前体和正在进行的细胞数量程序性细胞死亡将通过确定在同一肿瘤中测量通过检测 TRPM-2基因并通过测量他的凋亡指数。与此方法论，我们建议研究HCG的机制抑制DMBA诱导的大鼠乳腺癌的进展确定是否通过诱导细胞来调节肿瘤生长分化，抑制细胞增殖和/或激活程序性细胞死亡。我们还建议确定是否 HCG对肿瘤进展的抑制作用是直接影响肿瘤细胞上的激素由HCG与特定的结合作用 Lutropin-Choriogonadropin受体（LH-CG-R），该受体是否为治疗或通过HCG本身；最后，我们建议确定什么是抑制素对乳腺肿瘤的直接影响以及是否是 HCG对乳腺的分化作用的介体。这回答这些问题将有助于确定是否荷尔蒙诱导的分化是开发更多的合理机制预防癌症和治疗的理由基础。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Roscovitine induces cell death and morphological changes indicative of apoptosis in MDA-MB-231 breast cancer cells.

Roscovitine 诱导 MDA-MB-231 乳腺癌细胞死亡和指示细胞凋亡的形态变化。

DOI：
发表时间：
1999
期刊：
Cancer research
影响因子：
11.2
作者：
Mgbonyebi,OP;Russo,J;Russo,IH
通讯作者：
Russo,IH

Growth inhibition and activation of apoptotic gene expression by human chorionic gonadotropin in human breast epithelial cells.

人乳腺上皮细胞中人绒毛膜促性腺激素的生长抑制和凋亡基因表达的激活。

DOI：
发表时间：
1998
期刊：
Anticancer research.
影响因子：
0
作者：
Srivastava,P;Russo,J;Mgbonyebi,OP;Russo,IH
通讯作者：
Russo,IH

Biological and molecular basis of human breast cancer.

DOI：
10.2741/a335
发表时间：
1998-09
期刊：
Frontiers in bioscience : a journal and virtual library
影响因子：
0
作者：
J. Russo;Xiaoqi Yang;Y. Hu;Bove Ba;Yajue Huang;I. Silva;Q. Tahin;Y. Wu;N. Higgy;A. Zekri;I. Russo
通讯作者：
J. Russo;Xiaoqi Yang;Y. Hu;Bove Ba;Yajue Huang;I. Silva;Q. Tahin;Y. Wu;N. Higgy;A. Zekri;I. Russo

Toward a unified concept of mammary carcinogenesis.

争取乳腺癌发生的统一概念。