EFFECTS OF MELATONIN ON MAMMARY AND UTERINE TUMOR GROWTH

褪黑激素对乳腺癌和子宫肿瘤生长的影响

• 批准号: 3183722
• 负责人: DAVID BLASK
• 金额: $ 8.65万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-15 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3183722
• 关键词: benzanthracenes; breast neoplasms; chemical carcinogenesis; circadian rhythms; disease /disorder model; electron microscopy; estradiol; experimental brain lesion; gel electrophoresis; hormone receptor; hormone regulation /control mechanism; human tissue; laboratory rat; melatonin; neoplastic cell; neoplastic growth; neuroendocrine system; nitrosourea; pineal body; prolactin; protein biosynthesis; radioimmunoassay; steroid hormone metabolism; sulfotransferase; tissue /cell culture; uterus neoplasms

The long range goal of this research is to further elucidate and understand the mechanisms by which melatonin (Mel), the major hormone of the pineal gland, inhibits the proliferation of hormone-responsive breast cancer in vivo and in vitro in both animal and human models of breast cancer. The proposed studies will determine the effects of Mel and/or pinealectomy on the development and growth of carcinogen-induced breast cancers in female rats. Studies will address the hypothesis that Mel is inhibitory while pinealectomy is stimulatory to mammary tumorigenesis. Certain experiments will test whether Mel is a more effective inhibitor of breast cancer growth when administered during either the initiation or promotional phases of carcinogenesis. Moreover, these experiments will determine whether there is a diurnal rhythm of responsiveness to the inhibitory effects of Mel in the animal models of human breast cancer. Additional studies will determine whether replacement of the daily Mel signal in pinealectomized rats attenuates the tumor-promoting effects of pinealectomy. Blood levels of estradiol (E2), prolactin (PRL) as well as E2 and PRL receptor binding in tumor tissue will be correlated with the effects of Mel and/or pinealectomy on mammary tumorigenesis. Other studies will test the effects of Mel on the growth of established carcinogen-induced breast cancers in intact and hypophysectomized rats in response to E2 and/or PRL. Other in vitro studies will determine the effects of Mel directly on the growth, hormone binding, estrogen sulfotransferase activity and mitogenic protein synthesis/secretion of carcinogen-induced breast cancer cells as well as estrogen-responsive human breast cancer cells. These experiments will also examine the ultrastructural correlates of the Mel's inhibition of human breast cancer cell growth in vitro. Related studies will determine the effects of Mel on carcinogen-induced and human breast cancer cell growth in response to E2 and/or PRL. This research will increase our understanding of the neuroendocrine, peripheral endocrine and cellular-molecular mechanisms by which Mel inhibits breast cancer growth and may lead to the use of Mel as a new antineoplastic agent in the treatment of hormone-responsive human breast cancer.

这项研究的长期目标是进一步阐明和理解 松果体的主要激素褪黑激素 (Mel) 的作用机制 腺体，抑制激素反应性乳腺癌的增殖 乳腺癌动物和人类模型的体内和体外研究。 这 拟议的研究将确定梅尔和/或松果体切除术对 女性致癌物诱发乳腺癌的发生和生长 老鼠。 研究将解决梅尔具有抑制性的假设 松果体切除术会刺激乳腺肿瘤的发生。 某些实验 将测试梅尔是否是更有效的乳腺癌生长抑制剂 当在启动或推广阶段施用时 致癌作用。 此外，这些实验将确定是否存在 是对梅尔抑制作用的反应的昼夜节律 人类乳腺癌的动物模型。 额外的研究将 确定松果体切除后是否更换每日梅尔信号 大鼠减弱松果体切除术的肿瘤促进作用。 血液水平 雌二醇 (E2)、催乳素 (PRL) 以及 E2 和 PRL 受体结合 肿瘤组织中的含量与 Mel 和/或 松果体切除术对乳腺肿瘤发生的影响。 其他研究将测试效果 梅尔对已确定的致癌物诱发乳腺癌生长的影响 完整大鼠和垂体切除大鼠对 E2 和/或 PRL 的反应。 其他在 体外研究将确定梅尔对生长的直接影响， 激素结合、雌激素磺基转移酶活性和促有丝分裂蛋白 致癌物诱导的乳腺癌细胞的合成/分泌以及 雌激素反应性人类乳腺癌细胞。 这些实验也将 检查梅尔对人类的抑制的超微结构相关性 乳腺癌细胞在体外的生长。 相关研究将确定 Mel 对致癌物诱导的和人乳腺癌细胞生长的影响 对 E2 和/或 PRL 的反应。 这项研究将增加我们的理解 神经内分泌、外周内分泌和细胞分子 Mel 抑制乳腺癌生长并可能导致 Mel作为新型抗肿瘤药物在治疗中的应用 激素反应性人类乳腺癌。