Shimizu Takahisa, Okayama Akiko, Inoue Toshihiro, Takeda Ken
Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki Noda-shi, Chiba 278-8510, Japan.
Oncol Rep. 2005 Aug;14(2):441-8.
Staurosporine induces neuronal differentiation and suppresses malignancy of human prostate cancer TSU-Pr1 cells. To investigate the mechanism underlying neuronal differentiation and suppression of malignancy, we used cDNA microarrays to examine gene expression profiles in TSU-Pr1 cells treated with staurosporine. mRNAs isolated from untreated and staurosporine-treated TSU-Pr1 cells were hybridised to microarrays consisting of approximately 9100 genes. Changes in gene expression were verified by Northern blot analysis. Staurosporine-responsive genes were involved in a variety of cellular functions including growth regulation, differentiation, replication, DNA repair, G2/M transition and inhibition of apoptosis. Interestingly, expression of genes associated with cell proliferation and malignancy, such as Cyr61 and CTGF, was reduced. Expression of CD73/NT5E, which is involved in neuronal differentiation, was increased. In the present study, we identified various staurosporine-responsive genes in TSU-Pr1 cells. Further studies of the roles of these genes may clarify the mechanisms underlying neuronal differentiation and inhibition of malignancy by staurosporine and identify better approaches for the prevention and treatment of prostate cancer.
星形孢菌素可诱导人前列腺癌TSU-Pr1细胞发生神经元分化并抑制其恶性增殖。为了探究神经元分化及恶性增殖抑制的潜在机制，我们使用cDNA微阵列来检测经星形孢菌素处理的TSU-Pr1细胞中的基因表达谱。从未经处理和经星形孢菌素处理的TSU-Pr1细胞中分离出的mRNA与包含约9100个基因的微阵列进行杂交。基因表达的变化通过Northern印迹分析进行验证。星形孢菌素反应性基因参与多种细胞功能，包括生长调节、分化、复制、DNA修复、G2/M期转换及凋亡抑制。有趣的是，与细胞增殖和恶性肿瘤相关的基因，如Cyr61和CTGF的表达降低。参与神经元分化的CD73/NT5E的表达增加。在本研究中，我们在TSU-Pr1细胞中鉴定出了多种星形孢菌素反应性基因。对这些基因作用的进一步研究可能会阐明星形孢菌素诱导神经元分化及抑制恶性增殖的机制，并为前列腺癌的预防和治疗找到更好的方法。
