Enhancement of c-erbA proto-oncogene expression by glucocorticoid hormones in S49.1 lymphoma cells

The modifications of the mRNA levels of the c-myc and c-erbA proto-oncogenes during the dexamethasone-induced decrease of S49.1 cell proliferation have been studied. The levels of c-myc mRNA decreased significantly between 3 and 18 h after dexamethasone (1 microM) treatment. In contrast, a significant increase in the levels of a 2.6 kb c-erbA mRNA was observed between 6 and 18 h after hormone treatment. Cycloheximide treatment of S49.1 cells increased the levels of c-erbA RNA and overcome the enhancing effect of dexamethasone on the expression of this proto-oncogene, suggesting that ongoing protein synthesis is necessary to elicit this hormone effect. The associated decrease of cell proliferation and changes in c-myc and c-erbA mRNA levels after dexamethasone treatment suggest that such oncogenes might be involved in the dexamethasone-mediated control of lymphoid cell growth.     

Glucocorticoid effect on oncogene/growth gene expression in human T lymphoblastic leukemic cell line CCRF-CEM. Specific c-myc mRNA suppression by dexamethasone

Glucocorticoids induce growth inhibition and eventually cause cell lysis in certain sensitive leukemic cells. To investigate how glucocorticoids interact with cell growth pathways, we studied the expression of 14 growth-related genes in dexamethasone-treated CEM-C7A cells, a steroid-sensitive clone of the CCRF-CEM cell line, and in several closely related clones. The 14 genes studied were chosen to represent four different levels of mitogenic signal transduction. Detectable mRNA levels were found for 8 of the 14 genes, but among these only c-myc expression was obviously suppressed by dexamethasone. The c-myc mRNA levels declined abruptly during the first 12 h after addition of 1 microM dexamethasone, and maximal suppression occurred by 18 h. This change was not seen in the C7A controls, in the glucocorticoid-resistant, receptor-deficient clone ICR-27, or in the glucocorticoid-resistant, receptor-positive clone C1. H.10, a hybrid clone between C1 and ICR-27, showed restoration of the sensitive phenotype, and in H.10 cells the c-myc mRNA was also suppressed by dexamethasone. Our results suggest that: 1) functional glucocorticoid receptor is required for inducing c-myc suppression. 2) In dexamethasone-resistant cells with functional receptors c-myc is not suppressed. 3) The growth arrest induced by glucocorticoids correlates with, and may be regulated via, suppression of c-myc expression.     

Differential control of proto-oncogene c-myc and c-fos expression in lymphocytes and fibroblasts.

In lymphocytes stimulated with the mitogen phytohaemagglutinin, an inhibitor of the enzyme ADP-ribosyltransferase (ADPRT) completely blocks the proliferative response and the increase in expression of the proto-oncogene c-myc without affecting c-fos significantly. Conversely, in fibroblasts the serum-induced growth is not affected by the ADPRT inhibitor, and both oncogenes are dramatically super-induced. Hence there are differences between lymphocyte and fibroblast early responses to mitogenic stimulation and also between regulation of c-fos and c-myc gene expression.     

c-myc gene expression in human cells is controlled by glucose

The c-myc oncogene is implicated in normal growth and differentiation processes. Human cell lines IM9 and HepG2 stably cultured at "low" glucose concentrations (5.5 mM) show c-myc mRNA levels 3-4 times higher than cells cultured at "high" glucose concentrations (25 nM). D-fructose (a metabolizable exose) substitutes for D-glucose in reducing c-myc expression while 3-ortho-methylglucose (a non metabolizable exose) is uneffective. c-myc expression is up-regulated (by PMA) or down-regulated (by dexamethasone and long-term exposure to FCS) in human cells cultured at "low" glucose but not in cells cultured at "high" glucose. We previously demonstrated that insulin receptor gene expression in human cell lines in enhanced by glucose. Therefore, glucose controls in an opposite way the expression of two genes important in the regulation of eukaryotic cell growth and differentiation.     

Expression of c-myc proto-oncogene in normal human intestinal epithelium

We studied the expression of the human c-myc proto-oncogene in normal human colon epithelium by both in situ hybridization and immunohistochemistry. c-myc was found to be expressed uniformly throughout the entire thickness of the colon epithelium. The present findings do not support the contention that the c-myc proto-oncogene is primarily expressed in proliferating intestinal epithelial cell compartments.     

Post-transcriptional restriction of human adenovirus expression in monkey cells.

Infection of the continuous simian cell lines CV-1 and BSC-1 with human adenovirus type 2 (Ad2) is abortive. However, the restriction of Ad2 reproduction in these cells can be overcome by increasing the Ad2 infectious dose or by coinfection with simian virus 40. Vero, another established simian cell line free of detectable endogenous simian virus 40 DNA, is not restricted in its ability to promote Ad2 growth even at low input multiplicities of Ad2 and in the absence of SV40 helper. The amount of structural Ad2 proteins in total cell extracts of enhanced BSC-1 cells is at least two orders of magnitude higher than that of unenhanced cells. In contrast, comparable quantities of Ad2 mRNA specifying these proteins are found in both the enhanced and the unenhanced cell. Both sets of mRNA can be translated in a cell-free system with equal efficiency.     

Apoptosis photoinduction by C60 fullerene in human leukemic T cells

The viability of normal (Wistar rat thymocytes) and transformed (human leukemia Jurkat cells) T cells after UV/Vis irradiation in the presence of pristine C60 fullerene was studied. The data obtained have shown that C60 fullerene exhibits cytotoxic effect against transformed T lymphocytes when combined with UV/Vis irradiation using mercury-vapor lamp (320-600 nm). C60 fullerene photocytotoxicity was not detected in thymocytes. C60-dependent photoinduced apoptosis of Jurkat cells was confirmed by DNA fragmentation and caspase-3 activation. No substantial increase of caspase-3 activation was observed in thymocytes treated with C60 fullerene plus irradiation, while antileukemic agent cytosine arabinoside was shown to induce caspase-3 activation both in Jurkat cells and thymocytes. The data obtained may be useful for development of photosensitizers for photodynamic therapy with selective action on leukemia cells.