Yamashita J, Ogawa M, Nomura K, Matsuo S, Inada K, Yamashita S, Nakashima Y, Saishoji T, Takano S, Fujita S
Department of Surgery II, Kumamoto University Medical School, Japan.
Cancer Res. 1993 Feb 1;53(3):464-7.
To investigate the potential regulation of endothelin 1 production in human breast cancer cells, we measured the release of immunoreactive endothelin 1 (ir-ET-1) from the MCF-7 and ZR-75-1 breast cancer cell lines in response to various agents including estrogen and tamoxifen as well as several cytokines. ir-ET-1 was detected in conditioned medium of MCF-7 cells and ZR-75-1 cells by specific radioimmunoassay. Among the agents tested, estrogen, tamoxifen, tumor necrosis factor, gamma-interferon, interleukin (IL) 1, and transforming growth factor beta had no effect on ir-ET-1 secretion by these breast cancer cells. However, IL-6 (20 ng/ml) treatment of MCF-7 cells and ZR-75-1 cells caused maximal increases in the amount of ir-ET-1 secreted into the culture medium to 206 and 314% of basal values after 6 h, respectively. This effect of IL-6 on ir-ET-1 secretion was inhibited by actinomycin D and cycloheximide, indicating that IL-6 stimulates de novo synthesis of ir-ET-1 at a transcriptional level. Reverse-phase high performance liquid chromatography coupled with radioimmunoassay in the conditioned medium from IL-6-treated cells revealed one major ir-ET-1 component corresponding to human standard ET-1. The present study demonstrates the potential for IL-6 to stimulate ir-ET-1 production in human breast cancer cells, which may participate in the process of acute phase reactant-like expression of this peptide and/or in the process of IL-6 enhanced breast cancer cell motility, the latter being recently clarified.
为研究人乳腺癌细胞中内皮素1产生的潜在调节机制，我们检测了MCF-7和ZR-75-1乳腺癌细胞系对包括雌激素、他莫昔芬以及几种细胞因子在内的多种试剂的反应中免疫反应性内皮素1（ir-ET-1）的释放情况。通过特异性放射免疫测定法在MCF-7细胞和ZR-75-1细胞的条件培养基中检测到了ir-ET-1。在所测试的试剂中，雌激素、他莫昔芬、肿瘤坏死因子、γ-干扰素、白细胞介素（IL）1和转化生长因子β对这些乳腺癌细胞的ir-ET-1分泌没有影响。然而，用IL-6（20 ng/ml）处理MCF-7细胞和ZR-75-1细胞后，6小时内培养基中分泌的ir-ET-1量分别最大增加至基础值的206%和314%。放线菌素D和环己酰亚胺抑制了IL-6对ir-ET-1分泌的这种作用，表明IL-6在转录水平上刺激了ir-ET-1的从头合成。对IL-6处理细胞的条件培养基进行反相高效液相色谱结合放射免疫测定，发现一种主要的ir-ET-1成分与人标准ET-1相对应。本研究证明了IL-6刺激人乳腺癌细胞中ir-ET-1产生的可能性，这可能参与了该肽急性期反应物样表达过程和/或IL-6增强乳腺癌细胞运动性的过程，后者最近已得到阐明。
