PROLACTIN REGULATION OF PROSTATE CITRATE PRODUCTION

前列腺癌现在是男性癌症死亡的第二大原因， 并结合良性前列腺增生症，现在代表了领先的 人类中的肿瘤疾病。在人类中，前列腺具有独特的 产生和分泌超高水平的柠檬酸的功能 酸。前列腺癌的主要特征是 产生柠檬酸的前列腺上皮细胞向恶性转化的研究 不能产生柠檬酸盐的细胞。我们的总体目标是 阐明和理解独特的代谢关系 描述前列腺细胞实现这一功能的能力； 了解催乳素和其他激素调节的机制 这一主要功能；阐明代谢和荷尔蒙变化 与前列腺癌相关；并将此信息用于新的 前列腺癌的诊断、预防和治疗方法 肿瘤。现在已经证实，催乳素是一种重要的 前列腺生柠檬酸的调节剂。这样做的具体目的是 计划是阐明催乳素调节的机制 正常前列腺上皮细胞的柠檬酸合成。少校 需要解决的关系是催乳素调节的机制 线粒体天冬氨酸氨基转移酶和丙酮酸脱氢酶 (PDH)E1pha，参与前列腺癌合成的两个关键酶。 拟议研究的重点将集中在催乳素对 MAAT和E1α基因的表达及蛋白激酶C的作用 (PKC)。一旦这些关系与正常的前列腺建立起来 大鼠前列腺外侧受累细胞中“催乳素-PKC-基因”的作用 人恶性前列腺细胞(LNCaP，PC-4DU-145)的调控 已经成立了。这将是第一次协调一致地描述 人前列腺上皮细胞中与柠檬酸相关的代谢。

Prostate cancer is now the second leading cause of cancer deaths in males, and combined with benign prostatic hyperplasia, now represents the leading neoplastic disease in man. In humans, the prostate gland has the unique function of producing and secreting extraordinarily high levels of citric acid. The major distinguishing characteristic of prostate cancer is the transformation of citrate producing prostate epithelial cells to malignant cells which are incapable of producing citrate. Our broad objectives are to elucidate and to understand the unique metabolic relationships which characterize the ability of prostate cells to achieve this function; to understand the mechanisms by which prolactin and other hormones regulate this major function; to elucidate the metabolic and hormonal alterations associated with prostate neoplasms; and to use this information for new approaches in the diagnosis, prevention, and treatment of prostate neoplasms. It has now been established that prolactin is an important regulator of prostate citrate production. The specific aims of this program is to elucidate the mechanisms by which prolactin regulates citrate synthesis of normal prostate epithelial cells. The major relationship to be addressed is the mechanism by which prolactin regulates mitochondrial aspartate aminotransferase (mAAT) and pyruvate dehydrogenase (PDH) E1alpha, the two key enzymes involved in prostate citrate synthesis. The focus of the proposed studies will be on prolactin regulation of expression of the mAAT and E1alpha genes and the role of protein kinase C (PKC). Once these relationships are established with normal prostate cells involving rat lateral prostate, the role of "prolactin-PKC-gene regulation" in human malignant prostate cells (LNCaP, PC-4 Du-145) will be established. This will represent the first concerted characterization of citrate-related metabolism in human prostate epithelial cells.