Guillem J G, Levy M F, Hsieh L L, Johnson M D, LoGerfo P, Forde K A, Weinstein I B
Comprehensive Cancer Center, Columbia University, New York, New York.
Mol Carcinog. 1990;3(2):68-74. doi: 10.1002/mc.2940030204.
Our previous work on protein kinase C (PKC) and colon cancer has shown altered levels of PKC activity in human colon tumors, as well as activation of PKC by colon tumor promoters such as bile acids. To understand further the role of PKC in colon carcinogenesis, we analyzed the expression of phorbin, a gene induced by PKC activation, in a series of different stages of human colon tumors. As shown by northern blot analyses of poly (A)+ RNA, higher levels of phorbin RNA were seen in 26 colon tumor samples than in their adjacent normal colonic mucosa. There also appeared to be a correlation between the abundance of phorbin RNA in the tumors and the extent of invasion (tumor-to-normal tissue phorbin RNA ratio = 4.2, 8.0, and 11.9 for Dukes' A, B, and C, respectively). Phorbin RNA was also abundant in a human colon cancer line (HT29). We also examined the expression of other mitogen-responsive genes (c-myc, ODC, and beta-actin) in a set of 19 colon tumor samples. All tumors displayed significant (mean 3.8-fold) increases in the level of c-myc RNA compared with their adjacent normal colonic mucosa. About 47% and 16% of these tumor samples also showed increased levels of ODC (mean 3.1-fold) and beta-actin (mean 1.6-fold) RNA, respectively. The increased levels of c-myc, ODC, and beta-actin RNA did not correlate with the extent of tumor invasion. Taken together, these results demonstrate that human colon tumors usually display increased levels of both phorbin and c-myc RNAs. The marked increases in phorbin RNA suggest that this could serve as a useful biomarker in studies on human colon cancer.
我们先前关于蛋白激酶C（PKC）与结肠癌的研究表明，人类结肠肿瘤中PKC活性水平发生改变，并且结肠肿瘤启动子（如胆汁酸）可激活PKC。为了进一步了解PKC在结肠癌发生中的作用，我们分析了佛波因（一种由PKC激活诱导的基因）在一系列不同阶段人类结肠肿瘤中的表达情况。通过对聚腺苷酸加尾（poly (A)+）RNA进行Northern印迹分析显示，在26个结肠肿瘤样本中，佛波因RNA的水平高于其相邻的正常结肠黏膜。肿瘤中佛波因RNA的丰度与侵袭程度之间似乎也存在相关性（对于Dukes' A、B和C期，肿瘤与正常组织的佛波因RNA比值分别为4.2、8.0和11.9）。佛波因RNA在人类结肠癌细胞系（HT29）中也很丰富。我们还检测了一组19个结肠肿瘤样本中其他有丝分裂原反应基因（c-myc、鸟氨酸脱羧酶（ODC）和β-肌动蛋白）的表达。与相邻的正常结肠黏膜相比，所有肿瘤的c-myc RNA水平均显著升高（平均为3.8倍）。这些肿瘤样本中约47%和16%的ODC（平均为3.1倍）和β-肌动蛋白（平均为1.6倍）RNA水平也分别升高。c-myc、ODC和β-肌动蛋白RNA水平的升高与肿瘤侵袭程度无关。综上所述，这些结果表明人类结肠肿瘤通常同时表现出佛波因和c-myc RNA水平的升高。佛波因RNA的显著升高表明，这可能作为人类结肠癌研究中的一种有用生物标志物。
