EFFECTS OF MELATONIN ON MAMMARY AND UTERINE TUMOR GROWTH

本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） 腺，抑制乳腺癌的增殖， 在乳腺癌的动物和人模型中的体内和体外。 的 拟议的研究将确定Mel和/或松果体切除术对 致癌物诱发的女性乳腺癌的发生和生长 大鼠 研究将解决这一假设，即梅尔是抑制，而 松果体切除对乳腺肿瘤的发生有促进作用。 某些实验 将测试梅尔是否是一种更有效的乳腺癌生长抑制剂 当在启动或促进阶段施用时， 致癌作用 此外，这些实验将确定是否有 是对Mel的抑制作用的反应性的昼夜节律， 人类乳腺癌的动物模型。 其他研究将 确定是否更换每日梅尔信号在松果体切除 大鼠减弱了松果体切除术的促肿瘤作用。 血液水平 雌二醇（E2）、催乳素（PRL）以及E2和PRL受体结合 在肿瘤组织中的作用将与Mel和/或 松果体切除术对乳腺肿瘤发生的影响 其他的研究将测试这些影响 Mel对已建立的致癌物诱导的乳腺癌生长的影响， 完整和垂体切除大鼠对E2和/或PRL的反应。 彼此 体外研究将确定Mel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 雌激素敏感的人乳腺癌细胞。 这些实验也将 检查超微结构相关的梅尔的抑制人类 乳腺癌细胞的体外生长。 相关研究将确定 Mel对致癌物诱导的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对 神经内分泌、外周内分泌和细胞分子 Mel抑制乳腺癌生长的机制，并可能导致 Mel作为一种新的抗肿瘤剂在治疗 对乳腺癌有免疫反应的人乳腺癌

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.