PREGNANCY ASSOCIATED PROTECTION AGAINST BREAST CANCER

与怀孕相关的乳腺癌预防措施

• 批准号: 6353295
• 负责人: FRANK J. TALAMANTES
• 金额: $ 3.37万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-10 至 2002-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353295
• 关键词: breast neoplasms; chemical related neoplasm /cancer; estradiol; female; hormone analog; hormone receptor; hormone regulation /control mechanism; laboratory rat; mammary gland; methylnitrosourea; neoplasm /cancer transplantation; ovariectomy; ovary; pregnancy; progesterone; prolactin; radioimmunoassay; reproductive hormone; somatotropin; steroid biosynthesis

DESCRIPTION: (adapted from the investigator's abstract) Pregnancy provides significant protection against breast cancer development in women that give birth before the age of 20 years. Similarly, parous rats are refractory to chemically induced mammary tumorigenesis. The mechanisms by which parity affects mammary cancer incidents will be investigated by the investigator and coworkers in this proposal using the rat as a model. Pregnancy is characterized by elevated concentrations in serum of hormones that regulate the development of the mammary gland and affect mammary carcinogenesis. This proposal examines the hypothesis that these hormonal changes, along with changes in the levels of hormone and growth factor receptors in the mammary gland, played a decisive role in reducing mammary gland susceptibility to carcinogenesis. In specific aim I, mammary tissue and isolated mammary epithelial cells from virgin rats previously treated with carcinogen, which are highly susceptible carcinogenesis, will be transplanted into gland-free pads of parous hosts, which are refractory to carcinogenesis, and vise versa to determine whether refractory mammary tissue becomes susceptible and if susceptible mammary tissue become refractory to carcinogenesis in an appropriate hormonal environment. In addition, isolated mammary tumor cells will be transplanted into gland-free fat pads of refractory and susceptible rats to determine whether the hormonal environment of both these groups of rats is capable of sustaining the growth of already established mammary tumors. In specific aim II, the role of growth hormone (GH), prolactin (PRL) and ovarian steroids in mediating the parity-associated refractoriness to chemically induced carcinogenesis will be examined. Somatostatin analog and bromocriptine will be used to reduce the circulating concentrations of GH and PRL, respectively, in virgin rats to the concentrations in parous rats. GH and PRL will be administered in osmotic pumps to parous rats to obtain the concentrations in serum of virgin animals. The GH and PRL manipulations will be carried out in intact rats and ovariectomized animals, untreated or treated with constant dosage of 17beta-estradiol and/or progesterone. All these experimental groups and untreated control groups will be injected with carcinogen and tumor incidence compared.

描述：(改编自调查人员的摘要)怀孕提供 显著预防乳腺癌发生的女性 在20岁之前出生的。类似地，分娩的大鼠对 化学诱导的乳腺肿瘤发生。奇偶性的机制 影响乳腺癌事件将由调查员调查 和同事在这项提案中使用老鼠作为模型。怀孕是 以血清中调节激素浓度升高为特征的 乳腺的发育和影响乳腺癌的发生。 这项提议检验了这些荷尔蒙变化的假设，以及 随着激素和生长因子受体水平的变化， 乳腺，在缩小乳腺中起着决定性的作用 致癌的易感性。在具体目标一中，乳腺组织和 原代大鼠乳腺上皮细胞的分离培养 致癌物，这是高度易感的致癌物质，将是 移植到产后寄主的无腺体衬垫中，这些衬垫对 癌的发生，反之亦然，以确定难治性乳腺 组织变得敏感，如果敏感的乳腺组织变得 在适当的荷尔蒙环境中不易致癌。在……里面 此外，分离的乳腺肿瘤细胞将被移植到无腺体中 对难治和易感大鼠的脂肪垫进行检测 这两组大鼠的荷尔蒙环境都能够维持 已经形成的乳腺肿瘤的生长。在具体目标二中， 生长激素(GH)、催乳素(PRL)和卵巢类固醇激素在卵巢发育中的作用 产次相关的不应性在化学诱导中的中介作用 我们将检查致癌情况。生长抑素类似物和溴隐亭将 用于降低GH和PRL的循环浓度， 分别在处女大鼠体内达到分娩大鼠体内的浓度。GH和 PRL将在渗透泵中给予产后大鼠，以获得 处女动物血清中的浓度。生长激素和催乳素的操作 将在完整的大鼠和去卵巢的动物身上进行，未经处理或 给予恒定剂量的17β-雌二醇和/或黄体酮治疗。全 这些试验组和未处理的对照组将注射 比较致癌物和肿瘤发病率。