WHV＼myc转基因小鼠肝癌发生过程中c—myc基因表达的双相性

目的：WHV／myc转基因小鼠其肝脏肿瘤的自然发生率很高，本研究旨在细胞水平探测WHV／myc转基因小鼠肝癌发生过程中。c-myc转染基因的表达方式和肝细胞的增殖活性。方法：用核酸分子原位杂交的方法，检测了WHV／myc转基因小鼠肝肿瘤形成的不同阶段肝组织中c-myc基因的表达，同时检测了细胞增殖标志-组蛋白H3-2mRNA的表达。结果：10天龄小鼠肝脏中c-myc转染基因呈中等程度的表达，伴随30％的肝细胞增殖。随后，该基因表达水平迅速降低，在2月龄、4月龄和9月龄小鼠的肝脏中均不能够检测出。此期间肝细胞的增殖活性亦处于低水平。c-myc转染基因的表达重新出现于肿瘤形成期，肝腺瘤和肝癌的表达方式和强度相仿。肝细胞的增殖活性在此期约为14％左右。结论：c-myc转染基因在小鼠出生后早期和肿瘤形成期的异常表达对肝肿瘤的发生和瘤细胞转化表型的维持可能具有重要意义。     

Expression and amplification of myc gene family in small cell lung cancer and its relation to biological characteristics

Eighteen small cell lung cancer (SCLC) lines (including nine lines established by this group) as well as 31 tumor samples from 23 SCLC patients were examined for the surface antigen phenotype and the expression and amplification of the myc gene family. The expression of NE-150 neuroendocrine, PE-35 panepithelial and OE-130 epithelial antigens corresponded well with the level of biomarkers of SCLC lines, i.e., the NE-150+/PE-35+/OE-130- phenotype corresponded to classic type, while the other phenotypes such as NE-150+/PE-35-/OE-130- to variant type. In tumor specimens, most classic SCLC (consisting of oat cell type and intermediate cell type, subtype a) showed NE-150+/PE-35+/OE-130- phenotype, while small cell-large cell carcinoma (intermediate cell type, subtype b) expressed various phenotypes. The amplification of the myc gene family was observed in nine out of 18 lines (50%) and five out of 23 patient tumors (22%). Higher levels of expression of either c-myc, N-myc, or L-myc were detected in 16 out of 18 lines (89%) and in five out of six patient tumors (83%), when compared with that of normal or fetal lung tissues. Thus, the higher expression without obvious myc gene amplification was observed. The cell lines and tumors with the amplified myc always expressed their corresponding myc genes. The results suggested that higher levels of expression of the myc gene family may play a significant role in the oncogenesis of SCLC. Amplification and/or high levels of expression of c-myc were observed not only in variant type SCLC lines, but also in classic type lines. Thus, they were not necessarily associated with distinct biomarkers of SCLC lines.     

Distribution of cells expressing myc proteins in human colorectal epithelium, polyps, and malignant tumors.

The myc gene family encodes nuclear phosphoproteins that are thought to play a role in the control of cellular proliferation and differentiation. We have undertaken an immunohistochemical study assessing the expression of myc gene family proteins in individual cells of normal colonic mucosa, colorectal polyps, and colorectal adenocarcinomas. We screened a panel of mouse monoclonal antibodies that we raised against recombinant human c-myc and N-myc proteins for recognition of myc proteins in paraffin tissue sections. Two of these antibodies, H120C69 and H8C150, were selected for indirect immunoperoxidase staining of tissue sections from 16 normal mucosas, 24 polyps, and 30 adenocarcinomas. In normal colon, about 25% of the cells in the lower one-third of the crypts of Lieberkühn stain for myc-related protein. This distribution resembles that of proliferating cells in the crypt. Benign hyperplastic polyps resemble normal mucosa in their myc staining pattern, with about 25% of the cells positive. In adenomatous polyps, the putative precursors of adenocarcinomas, from 50 to 100% of the cells stain positively for myc protein. In these cases, stained cells extend to the luminal surface, consistent with the previously reported expansion of the proliferation zone in these lesions. All adenocarcinomas examined had increased levels of myc protein relative to normal mucosa. The tumor cells exhibited markedly heterogeneous myc staining patterns, both among different tumors and, in some cases, within a single tumor. Comparison with Ki-67 monoclonal antibody staining indicates that myc protein expression in many tumors is uncoupled from cellular proliferation. Surprisingly, we observed increased numbers of myc-expressing cells and increased levels of myc protein in histologically normal colon directly adjacent to tumor, suggesting that many colorectal carcinomas secrete growth factors that activate gene expression in neighboring normal mucosa.     

Overexpression and amplification of the c-myc gene in mouse tumors induced by chemicals and radiations

We examined expression of the c-myc gene by the dot blot hybridization of total cellular RNA from mouse primary tumors induced by chemicals and radiations. Expression of the c-myc gene was found to be elevated in 69 cases among 177 independently induced tumors of 12 different types. DNA from tumors overexpressing the myc gene was analyzed by Southern blotting. No case of rearrangement was detected. However, amplification of the c-myc gene was found in 7 cases of primary sarcomas. These included 4 cases out of 24 methylcholanthrene-induced sarcomas and 3 cases out of 7 alpha-tocopherol-induced sarcomas. We also analyzed 8 cases of sarcomas induced by radiations, but could not find changes in the gene structure of the c-myc gene. Thus, our data indicate tumor type specificity and agent specificity of c-myc gene amplification.