Criss W E, Morris H P
Cancer Res. 1976 May;36(5):1740-3.
Adenylate cyclase systems were examined in purified membrane preparations from normal rat liver and several Morris hepatomas with differing growth rates. All tumor membrane preparations had lower relative specific activities than did liver preparations. Liver adenylate cyclase was stimulated by fluoride, glucagon and guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Membranes from two slow-growing hepatomas (hepatomas 20 and 21) contained adenylate cyclase activities which are also stimulated by each of these three modulators. Membrane adenylate cyclases from several fast-growing hepatomas (hepatomas 3924A, 7777, 5123tc, and 9618A2) were marginally stimulated by glucagon but were readily stimulated by fluoride and Gpp(NH)p. Examination of the highly specific binding of 125I-glucagon to the various membrane preparations revealed much less binding in all the tumor membranes than in liver membranes. More detailed kinetic examination of membranes prepared from liver, slow-growing hepatoma 21 (which had reasonable binding to and stimulation by glucagon), and fast-growing hepatoma 3924A (which had marginal binding to and stimulation by glucagon) revealed major differences in rates of cyclic adenosine 3':5'-monophosphate production in the absence and presence of glucagon, Gpp(NH)p, and glucagon plus Gpp(NH)p and in the combined alteration of magnesium:adenosine 5'-triphosphate ratio and temperatures. The different kinetic characteristics in the hepatoma adenylate cyclase systems may be due to different structural characteristics of the tumor membranes or may be due to altered hormonal receptors, catalytic units, or receptor-catalytic unit interrelationships within the tumor membrane.
对来自正常大鼠肝脏以及几种生长速率不同的莫里斯肝癌的纯化膜制剂中的腺苷酸环化酶系统进行了研究。所有肿瘤膜制剂的相对比活性均低于肝脏制剂。肝脏腺苷酸环化酶受到氟化物、胰高血糖素和鸟苷 - 5'- 基亚氨基二磷酸 [Gpp(NH)p] 的刺激。来自两种生长缓慢的肝癌（肝癌20和21）的膜含有腺苷酸环化酶活性，这三种调节剂中的每一种也能刺激该活性。来自几种生长迅速的肝癌（肝癌3924A、7777、5123tc和9618A2）的膜腺苷酸环化酶受到胰高血糖素的轻微刺激，但很容易受到氟化物和Gpp(NH)p的刺激。对125I - 胰高血糖素与各种膜制剂的高度特异性结合的研究表明，所有肿瘤膜中的结合都比肝膜中的少得多。对从肝脏、生长缓慢的肝癌21（对胰高血糖素有合理的结合和刺激）和生长迅速的肝癌3924A（对胰高血糖素只有轻微的结合和刺激）制备的膜进行更详细的动力学研究发现，在不存在和存在胰高血糖素、Gpp(NH)p以及胰高血糖素加Gpp(NH)p的情况下，以及在镁：腺苷 - 5'- 三磷酸比率和温度的联合改变中，环磷酸腺苷生成速率存在重大差异。肝癌腺苷酸环化酶系统中不同的动力学特征可能是由于肿瘤膜的不同结构特征，或者可能是由于肿瘤膜内激素受体、催化单位或受体 - 催化单位相互关系的改变。
