Lipoprotein-induced expression of the sis oncogene in human arterial endothelial cells.
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Endothelium, Vascular↗
Biomedical subjects
G Totzke
Publications and source records attributed to G Totzke.
Action of dihydropyridine calcium antagonists on early growth response gene expression and cell growth in vascular smooth muscle cells.
OBJECTIVE: Evidence suggests that calcium antagonists may suppress vascular smooth muscle cell (VSMC) growth and proliferation, which may be a crucial step in the pathogenesis of hypertension and atherosclerosis. DESIGN: The effects of the dihydropyridine calcium antagonists nifedipine, nitrendipine, nisoldipine, nimodipine and isradipine on cell growth induced by platelet-derived growth factor (PDGF)-AB and angiotensin II (Ang II), and expression of the transcription factors c-fos and early-growth response gene 1 (egr-1) were investigated. METHODS: Proliferation of VSMC in culture was measured by [3H]-thymidine incorporation into cell DNA and by cell count. Expression of c-fos and egr-1 messenger RNA (mRNA) was determined by the Northern blot technique. RESULTS: All of the calcium antagonists blunted the PDGF-induced rise in VSMC DNA synthesis. The inhibitory potency of isradipine on PDGF-stimulated DNA synthesis was approximately 10-fold that of the other calcium antagonists used, isradipine having a half-maximal inhibitory concentration (IC50) of (4.2 +/- 0.16) x 10(-7) mol/l. The calcium antagonists investigated also inhibited Ang II-induced DNA synthesis. Isradipine (10(-6) mol/l) completely abolished the PDGF-induced cell proliferation. Both PDGF (50 ng/ml) and Ang II (10(-7) mol/l) induced c-fos and egr-1 mRNA expression, having maximum effect after 30 min. In the case of c-fos, pre-incubation with 5 x 10(-6) mol/l isradipine led to a decrease in both Ang II- and PDGF-induced expression of this immediate-early gene. The expression of egr-1 was not affected by pre-incubation with 5 x 10(-6) mol/l isradipine. CONCLUSIONS: All calcium antagonists investigated in the present study inhibited cell growth. Isradipine was more potent in blocking growth factor-induced cell growth than the other calcium antagonists studied. The inhibitory effect of the dihydropyridine calcium antagonists appears to be dependent on the expression of c-fos.
Animals↗
Different patterns of inducible nitric oxide synthase gene expression in ovarian carcinoma cell lines.
BACKGROUND: Stimulation of inducible nitric oxide synthase (iNOS) and release of nitric oxide by tumor cells may play a critical role in cancer development, either by exhibiting tumoricidal effects or by promoting tumor progression. MATERIALS AND METHODS: In the present study, we investigated four ovarian carcinoma cell lines with respect to their iNOS expressing characteristics. RESULTS: Following incubation with interferon-gamma, tumor necrosis factor-alpha and interleukin-1 beta, a marked stimulation of iNOS gene expression was found in SKOV-6 and OVCAR-3 cells, while only minor iNOS synthesis was detectable in HOC-7. Time-dependent accumulation of nitrite/nitrate in the culture supernatant indicated that the three cell lines were stimulated to produce and release nitric oxide. In contrast, no NO generation was observed in the fourth cell line under investigation, 2774. CONCLUSION: Due to the growth regulatory functions attributed to NO, variations in NO production may be of importance e.g. following interferon-gamma therapy in patients with ovarian cancer.
Female↗