NEUROENDOCRINE INFLUENCES ON MAMMARY CANCER

神经内分泌系统已被证明在疾病的发生和发展中发挥作用。 人类和实验性乳腺癌的生长。然而，仍然有 关于内分泌反应机制还有很多有待了解的地方 参与调控这些肿瘤。一个神经内分泌腺，松果体， 通过其荷尔蒙褪黑素已多次被证明是抑制 致癌物诱导的乳腺肿瘤发生，有明显的例子 其对人乳腺癌细胞增殖有抑制作用。机制(S) 褪黑素是如何抑制乳腺癌生长的尚不清楚。然而， 几项研究指出褪黑素对雌激素的调节作用 受体表达。随着cDNAs探针和单抗的出现 人类雌激素受体的抗体，以及基因和蛋白质的抗体 是受雌激素控制的，现在提出一个全面的项目， 将检测生长参数和雌激素受体的表达 乳腺癌细胞对褪黑素的反应，并将这些相互关联 结果随着已知雌激素调节生长因子的表达。 提出了五项研究，旨在回答以下问题 关于褪黑素在人的生长和生理中的作用的问题 人乳腺癌：(1)褪黑素对人乳腺癌生长的抑制作用 人乳腺癌通过细胞自身的内分泌反应系统介导 和/或通过血清生长因子？(2)褪黑素改变雌激素吗？ 受体的表达，如果是，在什么水平上(S)？(3) 褪黑素诱导雌激素受体表达导致雌激素变化 调节蛋白和生长因子？(4)褪黑素抑制生长吗？ 乳腺癌细胞通过不受雌激素调节的机制？(5) 褪黑素的体内效力是否与其体外作用相比较？ 原位抑制乳腺肿瘤细胞生长的水平是什么？ 该项目将提供这些问题的答案，并将 最终确定该基因的生物学和功能意义 松果体及其激素褪黑激素对松果体生长的影响 雌激素敏感型乳腺癌。

The neuroendocrine system has been shown to play a role in the genesis and growth of human and experimental mammary cancer. However, there is still much that remains to be learned regarding endocrine response mechanisms involved in regulating these tumors. One neuroendocrine gland, the pineal, via its hormone melatonin has repeatedly been shown to be inhibitory to carcinogen-induced mammary tumorigenesis, and there are clear examples of its inhibition of human breast cancer cell proliferation. The mechanism(s) by which melatonin inhibits breast cancer growth is not known. However several studies point to a regulatory influence of melatonin on estrogen receptor expression. With the availability of cDNA probes and monoclonal antibodies to the human estrogen receptor, as well as to genes and proteins which are estrogen regulated, a comprehensive project is now proposed that will examine the growth parameters and estrogen receptor expression of breast cancer cells in response to melatonin, and will correlate these results with the expression of known estrogen regulated growth factors. Five studies are proposed which are designed to answer the following questions regarding the role of melatonin in the growth and physiology of human breast cancer: (1) Are the growth inhibitory effects of melatonin on human breast cancer mediated thru the cell's own endocrine response system and/or thru serum growth factors? (2) Does melatonin alter estrogen receptor expression and, if so, at what level(s)? (3) Does alteration of estrogen receptor expression by melatonin result in changes in estrogen regulated proteins and growth factors? (4) Does melatonin inhibit growth of breast cancer cells via mechanisms which are not estrogen regulated? (5) Does the in vivo potency of melatonin compare with its in vitro action, and at what level does inhibition of mammary tumor cell growth occur in situ? This project will provide the answers to these questions and will ultimately determine the biological and functional significance of the pineal gland and its hormone melatonin in altering the growth of estrogen-responsive breast cancer.