Wali R K, Baum C L, Bolt M J, Dudeja P K, Sitrin M D, Brasitus T A
Department of Medicine, University of Chicago Hospitals and Clinics, IL 60637.
Biochim Biophys Acta. 1991 Mar 19;1092(1):119-23. doi: 10.1016/0167-4889(91)90185-z.
Recent studies by our laboratory have indicated that alterations in protein kinase C activity may be involved in the early stage(s) of malignant transformation in the 1,2-dimethylhydrazine model of colonic adenocarcinoma. In order to further evaluate the possible role of protein kinase C in this multistage process, rats were given subcutaneous weekly injections of this procarcinogen (20 mg/kg body weight) or diluent for 26 weeks. One week after receiving the last injection, animals were killed and control colonic tissue, tumor tissue and tissue at least 1 cm away from these tumors ('uninvolved mucosa') were harvested. The activity and distribution of protein kinase C in the cytosolic and membrane fractions of these preparations as well as their 1,2-diacylglycerol mass were then examined and compared. The results of these studies demonstrated that: (1) total protein kinase C activity was reduced by approximately 35% and 60%, respectively, in the 'uninvolved' colonic mucosa and tumors of carcinogen-treated rats compared to their control counterpart values; (2) in the 'uninvolved' mucosa, this decrease in total activity was secondary to a decrease solely in cytosolic protein kinase C, whereas, in tumors both membrane and cytosolic activities were reduced; and (3) 1,2-diacylglycerol mass was significantly increased in colonic tumors versus control values. Based on these findings, it would appear that alterations in the cellular distribution and total activity of protein kinase C, possibly secondary to increases in 1,2-diacylglycerol mass, may also play a role in the latter stage(s) of malignant transformation in this experimental model.
我们实验室最近的研究表明，蛋白激酶C活性的改变可能参与了1,2 - 二甲基肼诱导的结肠腺癌模型恶性转化的早期阶段。为了进一步评估蛋白激酶C在这一多阶段过程中的可能作用，给大鼠每周皮下注射这种致癌物（20毫克/千克体重）或稀释剂，持续26周。在最后一次注射后一周，处死动物并采集对照结肠组织、肿瘤组织以及距这些肿瘤至少1厘米的组织（“未受累黏膜”）。然后检测并比较这些制剂的胞质和膜部分中蛋白激酶C的活性、分布及其1,2 - 二酰基甘油含量。这些研究结果表明：（1）与对照值相比，致癌物处理大鼠的“未受累”结肠黏膜和肿瘤中，总蛋白激酶C活性分别降低了约35%和60%；（2）在“未受累”黏膜中，总活性的降低仅是由于胞质蛋白激酶C的减少，而在肿瘤中，膜和胞质活性均降低；（3）结肠肿瘤中的1,2 - 二酰基甘油含量与对照值相比显著增加。基于这些发现，似乎蛋白激酶C的细胞分布和总活性的改变，可能继发于1,2 - 二酰基甘油含量的增加，在该实验模型的恶性转化后期阶段也可能起作用。
