Effect of a mammary-derived growth inhibitor on the expression of the oncogenes c-fos, c-myc and c-ras

A mammary-derived growth inhibitor (MDGI) inhibits the resumption of growth of stationary Ehrlich ascites carcinoma (EAC) cells in vitro. The present study shows that the resumption of growth is accompanied by a rapid increase of the steady state mRNA level of the proto-oncogenes c-fos, c-myc and c-ras, which is reduced by MDGI. EAC cells from the exponential growth phase insensitive to MDGI did not show a reduced RNA expression. The effect of MDGI represents a novel activity at the level of gene expression and suggests a link to exist between growth inhibition and the reduction of c-fos, c-myc and c-ras expression.     

Regulated expression of the c-myb and c-myc oncogenes during erythroid differentiation

We have investigated the expression of the genes c-myb, c-myc, and alpha globin in murine erythroid cells at different stages of development, in viral-induced erythroleukemias, as well as in two mouse erythroleukemia cell lines that can be induced to terminally differentiate when exposed to dimethylsulfoxide. We find that there is a reciprocal correlation between the cell's production of messenger RNA for c-myb and globin. c-myc message shows a similar but less dramatic decrease coincident with globin RNA production. Initially with the administration of an inducing agent, dimethylsulfoxide, there is a rapid decrease of myc and myb mRNA, which is followed by signs of differentiation in the induced culture. We conclude that these oncogenes function in early maturational stages of development of these cells. In the erythroleukemic state these genes are down-regulated by forced differentiation and may play a direct role in influencing the state of differentiation of these cells.     

Translatability of a plant-mRNA strongly influences its accumulation in transgenic plants.

Current knowledge of parameters affecting RNA stability is very restricted in plants. Here we investigated factors which might contribute to the stability of a particular plant messenger RNA. To this end, insertion and deletion mutants were made in two different exons and an intron of the transcribed region of a well characterised patatin gene (pgT5). Mutant genes were expressed under the control of a strong leaf-stem specific promoter (ST-LS1) and analysed in vivo in transgenic tobacco plants. Northern analysis revealed the importance of the translatability of the mature messenger RNA with respect to its accumulation in transgenic plants. Enlargement of the 3' non-translated region by several hundred base-pairs reduced the steady state mRNA level slightly; the introduction of a stop codon leading to premature termination of translation of the RNA led to a dramatic decrease of the steady state mRNA level.     

Amplification of the expression of the c-myc oncogene in bronchial epidermoid carcinoma in man

Squamous cell lung carcinomas from 10 untreated patients were examined for the state of the oncogene c-myc. Blot hybridization experiments have demonstrated the amplification of the oncogene of about six fold in only one tumor. The oncogene amplification was not detected in normal tissues of patients. The analysis of RNA by Northern blot revealed the presence in the seven tumors examined of a 2.4 kb c-myc RNA band. The level of c-myc expression evaluated by dot blot analysis was 5 to 14 fold greater in tumors than that of histologically normal lung of the same patients.     

Human immunodeficiency virus infection of monoblastoid cells: cellular differentiation determines the pattern of virus replication.

Stringent control of human immunodeficiency virus (HIV) replication was observed in the human monoblastoid cell line U937. A low-multiplicity infection of these cells by the LAV1 strain of HIV was productive for 2.5 days; then virus replication became restricted and no further evidence of virion production was observed. The dramatic decrease in HIV production was due in part of reduced accumulation of cytoplasmic viral RNA and occurred in the absence of evident cytopathic effects. In contrast, infected cells induced to differentiate by phorbol ester, vitamin D3, or lymphokine supernatant did not release markers of HIV despite the accumulation of significant levels of cytoplasmic viral RNA. HIV infection altered the pattern of c-myc RNA accumulation in U937 cells. Expression of this gene changes normally in response to the state of cellular differentiation; in infected cells the level of c-myc expression was correlated to the levels of viral RNA accumulation and not to cellular differentiation. These results suggest that restricted replication of HIV in monocytes might be an important mechanism of virus persistence and demonstrate a relationship between HIV replication and monocyte differentiation.