Barnard G F, Staniunas R J, Bao S, Mafune K, Steele G D, Gollan J L, Chen L B
Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, MA 02115.
Cancer Res. 1992 Jun 1;52(11):3067-72.
To search for differentially expressed gene products in selected cancers of endodermal origin, cDNA libraries derived from mRNA in human hepatocellular carcinoma and adjacent grossly normal tissue were generated. From these parent libraries, subtracted cDNA libraries of tumor minus normal and normal minus tumor tissues were constructed. After screening these subtracted libraries by +/- hybridization, a cDNA clone that is overexpressed in hepatocellular carcinoma and encodes the human acidic ribosomal phosphoprotein P0 (P0) was identified. We then evaluated the expression of this phosphoprotein P0 in human colon carcinoma samples. Surgical specimens of primary tumors and liver metastases were examined by Northern hybridization of total RNA with one of 2 32P-labeled P0 probes. The mRNA level of the P0 was greater in primary colon carcinoma than in paired adjacent normal colonic epithelium in 36 of 38 cases; the mean tumor/normal ratio was 2.7 (range, up to 13). The tumor/normal ratio, when plotted against the Dukes' stage of disease, gave evidence for increasing P0 expression with increasing stage of colon carcinoma (P = 0.02). In all 8 cases of paired colon carcinoma metastatic to liver and 2 cases of paired primary hepatocellular carcinoma, the P0 mRNA level was greater in tumor than in adjacent normal liver tissue. The mean tumor/normal ratio was 4.0 (range, up to 11) for the colon cancers metastatic to liver and 4.2 for the primary hepatocellular carcinoma samples. These findings support a common increased expression of selected gene products in different tumors of endodermal origin and suggest that increased P0 expression, in line with certain other ribosomal proteins, may be associated with human colorectal cancer progression and biological aggressiveness.
为了在选定的内胚层起源癌症中寻找差异表达的基因产物,构建了源自人肝细胞癌和相邻大体正常组织中mRNA的cDNA文库。从这些亲本文库中,构建了肿瘤减正常和正常减肿瘤组织的扣除cDNA文库。通过+/-杂交筛选这些扣除文库后,鉴定出一个在肝细胞癌中过表达且编码人酸性核糖体磷蛋白P0(P0)的cDNA克隆。然后,我们评估了这种磷蛋白P0在人结肠癌样本中的表达。通过用两种32P标记的P0探针之一对总RNA进行Northern杂交,检测原发性肿瘤和肝转移灶的手术标本。在38例中的36例中,原发性结肠癌中P0的mRNA水平高于配对的相邻正常结肠上皮;肿瘤/正常平均比值为2.7(范围,高达13)。将肿瘤/正常比值与疾病的Dukes分期作图,结果表明结肠癌分期增加时P0表达增加(P = 0.02)。在所有8例配对的结肠癌肝转移病例和2例配对的原发性肝细胞癌病例中,肿瘤中P0 mRNA水平高于相邻正常肝组织。结肠癌肝转移的肿瘤/正常平均比值为4.0(范围,高达11),原发性肝细胞癌样本的该比值为4.2。这些发现支持了在不同的内胚层起源肿瘤中选定基因产物的共同表达增加,并表明P0表达增加,与某些其他核糖体蛋白一样,可能与人类结直肠癌的进展和生物学侵袭性相关。