Franklin R B, Zou J, Gorski E, Yang Y H, Costello L C
Department of Oral and Craniofacial Biological Sciences, University of Maryland, Dental School, Baltimore 21201, USA.
Mol Cell Endocrinol. 1997 Mar 14;127(1):19-25. doi: 10.1016/s0303-7207(96)03972-x.
Citrate production is a major physiological function of the prostate that is regulated by testosterone and prolactin. Mitochondrial aspartate aminotransferase (mAAT) is a key enzyme in the metabolic pathway of prostate citrate production. In addition, prolactin stimulates expression of mAAT in the rat lateral prostate. In this report we establish the role of prolactin in the regulation of mAAT in two prostate cancer cell lines, LNCaP and PC-3. LNCaP cells respond to hormonal stimulation with increased secretion of prostate specific products. PC-3 cells, on the other hand, are testosterone independent and apparently do not respond to other growth factors either. Results showed that both LNCaP and PC-3 cells responded to prolactin with increased mAAT activity and an increased steady state level of mAAT mRNA. Prolactin also increased protein kinase C (PKC) activity in both these cell lines. Treatment of LNCaP and PC-3 cells with the phorbol ester 12-O-tetradecanoylphorbol (TPA) caused the same effect on mAAT activity and mRNA level as prolactin. The results suggest that the diacylglycerol-PKC signal transduction system mediates the prolactin effect on mAAT. In addition, these results also show that the prolactin effect on mAAT is independent of androgens since PC-3 cells reportedly lack androgen receptor expression. Thus, these results provide evidence that prolactin is a physiological regulator of prostate function in human as well as rat prostate. In addition, the results also show that though prostate cancer cells are androgen independent, they remain responsive to prolactin. This could have important implications for the treatment and management of prostate cancer.
柠檬酸生成是前列腺的一项主要生理功能，受睾酮和催乳素调节。线粒体天冬氨酸转氨酶（mAAT）是前列腺柠檬酸生成代谢途径中的关键酶。此外，催乳素可刺激大鼠前列腺外侧叶中mAAT的表达。在本报告中，我们确定了催乳素在两种前列腺癌细胞系LNCaP和PC-3中对mAAT的调节作用。LNCaP细胞对激素刺激有反应，前列腺特异性产物分泌增加。另一方面，PC-3细胞不依赖睾酮，显然也不响应其他生长因子。结果显示，LNCaP和PC-3细胞对催乳素均有反应，mAAT活性增加，mAAT mRNA稳态水平升高。催乳素还增加了这两种细胞系中的蛋白激酶C（PKC）活性。用佛波酯12-O-十四酰佛波醇（TPA）处理LNCaP和PC-3细胞，对mAAT活性和mRNA水平产生了与催乳素相同的影响。结果表明，二酰甘油-PKC信号转导系统介导了催乳素对mAAT的作用。此外，这些结果还表明，催乳素对mAAT的作用不依赖雄激素，因为据报道PC-3细胞缺乏雄激素受体表达。因此，这些结果提供了证据，证明催乳素是人类以及大鼠前列腺中前列腺功能的生理调节因子。此外，结果还表明，尽管前列腺癌细胞不依赖雄激素，但它们仍对催乳素作出反应。这可能对前列腺癌的治疗和管理具有重要意义。
