Svec J, Svec P, Halcak L, Thurzo V
J Cancer Res Clin Oncol. 1982;103(1):55-67. doi: 10.1007/BF00410306.
The regulation of murine mammary tumor virus (MuMTV) production by mammotropic hormones, hormonomimetic substances, and cyclic nucleotides was investigated. The virus produced in control and treated mammary tumor cell cultures was quantitated by measuring the supernatant reverse transcriptase activity in exogenous reaction using poly(rC).oligo(dG) as template-primer. Two days after exposure, the synthetic glucocorticoid, dexamethasone (DXMT), increased spontaneous MuMTV production at optimal concentration (0.1 mumol) up to ten times. Dibutyryl derivative of cyclic AMP had no effect on spontaneous MuMTV production, whereas the drug potentiated suboptimal concentrations of the glucocorticoid. Natural prostaglandins, potent agonists of adenylate cyclase catalyzing intracellular synthesis of cyclic AMP, enhanced both basal (up to five times) and DXMT-stimulated (up to 1.6 times) MuMTV replication. The MuMTV-stimulating activity of prostaglandins decreased in the order of PGA1 greater than PGE1 greater than PGB1 greater than PGF2 alpha. Prostaglandins can be replaced partially by norepinephrine and isoproterenol by enhancing the DXMT-mediated MuMTV stimulation, whereas these drugs remained without effect on spontaneous MuMTV production. Theophylline, an antagonist of cAMP-phosphodiesterase converting cAMP to AMP, enhanced the virus-stimulating activity of DXMT as well as of prostaglandins. The enhancement of MuMTV production by adenylate cyclase agonists do not correlate absolutely with the estimates of intracellular cAMP levels, since the highest amounts of cAMP has been repeatedly observed in cells treated with PGE1 and norepinephrine. The results indicate that besides hormones, other hormone-like substances and cyclic nucleotides may be involved in the complex mechanism of hormone-regulated MuMTV genome expression.
研究了促乳腺激素、激素模拟物和环核苷酸对小鼠乳腺肿瘤病毒（MuMTV）产生的调节作用。通过使用聚（rC）·寡聚（dG）作为模板引物，在外源反应中测量上清液逆转录酶活性，对对照和处理过的乳腺肿瘤细胞培养物中产生的病毒进行定量。暴露两天后，合成糖皮质激素地塞米松（DXMT）在最佳浓度（0.1 μmol）下可使自发MuMTV产生增加至十倍。环磷酸腺苷的二丁酰衍生物对自发MuMTV产生没有影响，而该药物可增强糖皮质激素的次优浓度作用。天然前列腺素是催化细胞内环磷酸腺苷合成的腺苷酸环化酶的强效激动剂，可增强基础（高达五倍）和DXMT刺激（高达1.6倍）的MuMTV复制。前列腺素对MuMTV的刺激活性按PGA1＞PGE1＞PGB1＞PGF2α的顺序降低。通过增强DXMT介导对MuMTV的刺激，前列腺素可部分被去甲肾上腺素和异丙肾上腺素替代，而这些药物对自发MuMTV产生没有影响。茶碱是一种将环磷酸腺苷转化为腺苷酸的环磷酸腺苷磷酸二酯酶拮抗剂，可增强DXMT以及前列腺素的病毒刺激活性。腺苷酸环化酶激动剂对MuMTV产生的增强作用与细胞内环磷酸腺苷水平的估计并非绝对相关，因为在用PGE1和去甲肾上腺素处理的细胞中反复观察到最高量的环磷酸腺苷。结果表明，除激素外，其他激素样物质和环核苷酸可能参与了激素调节MuMTV基因组表达的复杂机制。
