PREGNANCY ASSOCIATED PROTECTION AGAINST BREAST CANCER

与怀孕相关的乳腺癌预防措施

• 批准号: 2895613
• 负责人: FRANK J. TALAMANTES
• 金额: $ 33.29万
• 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/2895613
• 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：（改编自研究者的摘要）怀孕提供 显着保护女性免受乳腺癌的发展 20岁之前出生。 同样，经产大鼠也难以抵抗 化学诱导乳腺肿瘤发生。 奇偶校验的机制 影响乳腺癌的事件将由研究者调查 和同事在这个提案中使用老鼠作为模型。 怀孕是 其特点是血清中调节激素的浓度升高 乳腺的发育并影响乳腺癌的发生。 该提案检验了以下假设：这些荷尔蒙变化随着 随着体内激素和生长因子受体水平的变化 乳腺，对减少乳腺起到决定性作用 致癌的易感性。 在具体目标 I 中，乳腺组织和 从先前接受过治疗的处女大鼠中分离出乳腺上皮细胞 致癌物质是极易致癌的物质， 移植到经产宿主的无腺垫中，该宿主对 癌变，反之亦然，以确定是否难治性乳腺 组织变得敏感，如果敏感的乳腺组织变得敏感 在适当的激素环境下不易致癌。 在 此外，分离的乳腺肿瘤细胞将被移植到无腺体中 难治性和易感性大鼠的脂肪垫以确定是否 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）和卵巢类固醇的作用 介导与奇偶相关的不应性到化学诱导 将检查致癌作用。 生长抑素类似物和溴隐亭将 用于降低 GH 和 PRL 的循环浓度， 分别是处女大鼠中的浓度和经产大鼠中的浓度。 生长激素和 PRL 将通过渗透泵给予经产大鼠以获得 原始动物血清中的浓度。 GH 和 PRL 操作 将在未经治疗或未处理的完整大鼠和卵巢切除动物中进行 用恒定剂量的 17β-雌二醇和/或黄体酮治疗。 全部 这些实验组和未治疗的对照组将注射 致癌物与肿瘤发生率的比较。