Barnard G F, Staniunas R J, Mori M, Puder M, Jessup M J, Steele G D, Chen L B
Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Cancer Res. 1993 Sep 1;53(17):4048-52.
The levels of a number of ribosomal protein mRNAs are reported to be increased in human colon cancer. We have assessed whether selected ribosomal protein mRNAs are overexpressed in other gastrointestinal malignancies, namely gastric and hepatocellular carcinomas. Subtracted complementary DNA libraries were generated from paired samples of human (a) colorectal carcinoma minus adjacent normal colonic mucosa and (b) hepatocellular carcinoma minus adjacent normal liver. Screening of approximately 3% of these library clones determined that ribosomal protein mRNAs encoding L18 and L37 (not previously reported) and P0 and S6 were overexpressed in one or the other library. Their complementary DNA inserts were then used as probes to evaluate their expression in a larger number of paired tumor/normal surgical samples of human colonic, gastric, and hepatocellular carcinomas, by Northern hybridization. The mRNA signal was greater in the colonic carcinoma than in paired adjacent normal colonic mucosa in 38 of 42 cases for P0 [tumor/normal (T/N) ratio = 3.0 +/- 0.3, mean +/- SE, P < 0.001] (G. F. Barnard, R. J. Staniunas, S. Bao, K. Mafune, J. L. Gollan, G. D. Steele, Jr., and L. B. Chen, Cancer Res., 52: 3067-3072, 1992), in 25 of 28 cases for L18 (T/N ratio = 3.7 +/- 0.5, P < 0.001), in 27 of 28 cases for L37 (T/N ratio = 5.3 +/- 0.4, P < 0.001), and in 24 of 28 cases for S6 (T/N ratio = 3.1 +/- 0.5, P < 0.01). The level of mRNA overexpression of L18 and S6 did not correlate with the Dukes' stage of disease. In hepatocellular carcinoma samples, using the same four ribosomal protein complementary DNA probes, only P0 mRNA was significantly increased (T/N ratio = 2.8 +/- 0.4, n = 6, P = 0.047). In gastric carcinoma samples, none of these mRNAs was increased (mean T/N ratios = 0.9-1.2, n = 6). Therefore, gastric and hepatocellular carcinomas do not overexpress the same ribosomal protein mRNAs as do colonic carcinoma.
据报道,多种核糖体蛋白mRNA的水平在人类结肠癌中有所升高。我们评估了特定的核糖体蛋白mRNA在其他胃肠道恶性肿瘤(即胃癌和肝细胞癌)中是否过表达。从人类的配对样本中构建了扣除互补DNA文库,这些样本包括:(a) 结直肠癌减去相邻的正常结肠黏膜,以及 (b) 肝细胞癌减去相邻的正常肝脏。对这些文库中约3%的克隆进行筛选后确定,编码L18和L37(此前未报道)以及P0和S6的核糖体蛋白mRNA在其中一个文库中过表达。然后,将它们的互补DNA插入片段用作探针,通过Northern杂交评估它们在大量人类结肠癌、胃癌和肝细胞癌的配对肿瘤/正常手术样本中的表达情况。在42例样本中有38例,P0的mRNA信号在结肠癌中比配对的相邻正常结肠黏膜中更强 [肿瘤/正常(T/N)比值 = 3.0 +/- 0.3,平均值 +/- 标准误,P < 0.001] (G.F. 巴纳德、R.J. 斯塔纽纳斯、S. 鲍、K. 马富内、J.L. 戈兰、G.D. 斯蒂尔 Jr. 和L.B. 陈,《癌症研究》,52: 3067 - 3072,1992);在28例样本中有25例,L18的mRNA信号如此 [T/N比值 = 3.7 +/- 0.5,P < 0.001];在28例样本中有27例,L37的mRNA信号如此 [T/N比值 = 5.3 +/- 0.4,P < 0.001];在28例样本中有24例,S6的mRNA信号如此 [T/N比值 = 3.1 +/- 0.