PREGNANCY ASSOCIATED PROTECTION AGAINST BREAST CANCER

与怀孕相关的乳腺癌预防措施

• 批准号: 6081928
• 负责人: FRANK J. TALAMANTES
• 金额: $ 6.57万
• 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 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6081928
• 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：（改编自研究者摘要）妊娠提供 显著保护女性免受乳腺癌的发展， 在20岁之前出生。 类似地，经产大鼠对 化学诱导的乳腺肿瘤发生。 实现平等的机制 影响乳腺癌的事件将由研究者进行调查 和同事们用老鼠做模型的提议。 怀孕是 其特征在于血清中调节 影响乳腺的发育和乳腺癌的发生。 这项提议检验了这样一种假设，即这些荷尔蒙的变化，沿着 随着激素和生长因子受体水平的变化， 乳腺癌，在减少乳腺癌中起着决定性的作用 对致癌作用的敏感性。 在具体目标I中，乳腺组织和 来自先前用以下处理的未交配大鼠的分离的乳腺上皮细胞： 致癌物质，这是高度敏感的致癌作用，将是 移植到无腺体垫的parous主机，这是难治的， 致癌作用，反之亦然，以确定是否难治性乳腺癌 组织变得敏感，如果敏感的乳腺组织变得 在适当的激素环境中不易致癌。 在 此外，将分离的乳腺肿瘤细胞移植到无腺体的 脂肪垫的难治性和易感大鼠，以确定是否 这两组大鼠的激素环境能够维持 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）和卵巢类固醇在 介导化学诱导的奇偶校验相关的不应性 将检查致癌作用。 生长抑制素类似物和溴隐亭将 用于降低GH和PRL的循环浓度， 分别为未孕大鼠和经产大鼠的浓度。 GH和 PRL将在渗透泵中给予经产大鼠，以获得 未交配动物血清中的浓度。 GH和PRL操作 将在未处理的完整大鼠和卵巢切除动物中进行，或 用恒定剂量的17 β-雌二醇和/或孕酮治疗。 所有 这些实验组和未处理的对照组将注射 致癌物和肿瘤发生率进行比较。