scholarly journals IRF-1 reverts the transformed phenotype of oncogenically transformed cells in vitro and in vivo

Oncogene ◽  
2003 ◽  
Vol 22 (7) ◽  
pp. 1045-1056 ◽  
Author(s):  
Andrea Kröger ◽  
Andreas Dallügge ◽  
Sabine Kirchhoff ◽  
Hansjörg Hauser
Keyword(s):  
Transformed Cells

Andrographolide Sensitizes Ras-Transformed Cells to Radiation in vitro and in vivo

2010 ◽  
Vol 77 (4) ◽  
pp. 1232-1239 ◽  
Author(s):  
Shih-Kai Hung ◽  
Ling-Chien Hung ◽  
Cheng-Deng Kuo ◽  
Kuan-Yi Lee ◽  
Moon-Sing Lee ◽  
...  
Keyword(s):  
Transformed Cells

Genomic and metabolomic analysis of step-wise malignant transformation in human skin fibroblasts

2019 ◽  
Vol 41 (5) ◽  
pp. 656-665
Author(s):  
Anastasia Kariagina ◽  
Sophia Y Lunt ◽  
J Justin McCormick
Keyword(s):  
Malignant Transformation ◽  
Human Fibroblasts ◽  
Glucose Consumption ◽  
Tca Cycle ◽  
Transformed Cells ◽  
Aminooxyacetic Acid ◽  
Malignant Cells ◽  
The Impact

Abstract Metabolic changes accompanying a step-wise malignant transformation was investigated using a syngeneic lineage of human fibroblasts. Cell immortalization was associated with minor alterations in metabolism. Consecutive loss of cell cycle inhibition in immortalized cells resulted in increased levels of oxidative phosphorylation (OXPHOS). Overexpression of the H-Ras oncoprotein produced cells forming sarcomas in athymic mice. These transformed cells exhibited increased glucose consumption, glycolysis and a further increase in OXPHOS. Because of the markedly increased OXPHOS in transformed cells, the impact of a transaminase inhibitor, aminooxyacetic acid (AOA), which decreases glutamine influx to the tricarboxylic acid (TCA) cycle, was tested. Indeed, AOA significantly decreased proliferation of malignantly transformed fibroblasts and fibrosarcoma-derived cells in vitro and in vivo. AOA also decreased proliferation of cells susceptible to malignant transformation. Metabolomic studies in normal and transformed cells indicated that, in addition to the anticipated effect on the TCA cycle, AOA decreased production of nucleotides adenosine triphosphate (ATP) and uridine monophosphate. Exogenous nucleotides partially rescued decreased proliferation of the malignant cells treated with AOA. Our data indicate that AOA blocks several metabolic pathways essential for growth of malignant cells. Therefore, OXPHOS may provide important therapeutic targets for treatment of sarcoma.

scholarly journals Protein Kinase Cζ Represses the Interleukin-6 Promoter and Impairs Tumorigenesis In Vivo

2008 ◽  
Vol 29 (1) ◽  
pp. 104-115 ◽  
Author(s):  
Anita S. Galvez ◽  
Angeles Duran ◽  
Juan F. Linares ◽  
Peterson Pathrose ◽  
Elias A. Castilla ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Interleukin 6 ◽  
Essential Role ◽  
Transformed Cells ◽  
Lung Carcinogenesis ◽  
Kinase C ◽  
Deficient Mice ◽  
Gene Alterations

ABSTRACT Gene alterations in tumor cells that confer the ability to grow under nutrient- and mitogen-deficient conditions constitute a competitive advantage that leads to more-aggressive forms of cancer. The atypical protein kinase C (PKC) isoform, PKCζ, has been shown to interact with the signaling adapter p62, which is important for Ras-induced lung carcinogenesis. Here we show that PKCζ-deficient mice display increased Ras-induced lung carcinogenesis, suggesting a new role for this kinase as a tumor suppressor in vivo. We also show that Ras-transformed PKCζ-deficient lungs and embryo fibroblasts produced more interleukin-6 (IL-6), which we demonstrate here plays an essential role in the ability of Ras-transformed cells to grow under nutrient-deprived conditions in vitro and in a mouse xenograft system in vivo. We also show that PKCζ represses histone acetylation at the C/EBPβ element in the IL-6 promoter. Therefore, PKCζ, by controlling the production of IL-6, is a critical signaling molecule in tumorigenesis.

scholarly journals Src-transformed cells hijack mitosis to extrude from the epithelium

2018 ◽  
Author(s):  
Katarzyna A. Anton ◽  
Mihoko Kajita ◽  
Rika Narumi ◽  
Yasuyuki Fujita ◽  
Masazumi Tada
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Apical Part ◽  
Transformed Cells ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Initial Stage ◽  
Apical Extrusion

AbstractAt the initial stage of carcinogenesis single mutated cells appear within an epithelium. Mammalian in vitro experiments show that potentially cancerous cells undergo live apical extrusion from normal monolayers. However, the mechanism underlying this process in vivo remains poorly understood. Mosaic expression of the oncogene vSrc in a simple epithelium of the early zebrafish embryo results in apical extrusion of transformed cells. Here we find that during extrusion components of the cytokinetic ring are recruited to adherens junctions of transformed cells, stimulating formation of a misoriented pseudo cytokinetic ring. During extrusion, the ring constricts and separates the basal from the apical part of the cell releasing both from the epithelium. This process requires cell cycle progression and occurs immediately after vSrc-transformed cell enters mitosis. To achieve extrusion, vSrc coordinates cell cycle progression, junctional integrity, cell survival and apicobasal polarity. Without vSrc, modulating these cellular processes reconstitutes vSrc-like extrusion, confirming their sufficiency for this process.

Restriction of the in vitro and in vivo tyrosine protein kinase activities of pp60c-src relative to pp60v-src

1985 ◽  
Vol 5 (10) ◽  
pp. 2753-2763
Author(s):  
P M Coussens ◽  
J A Cooper ◽  
T Hunter ◽  
D Shalloway
Keyword(s):  
Protein Kinase ◽  
Specific Activity ◽  
Cellular Protein ◽  
Transformed Cells ◽  
Exogenous Substrate ◽  
Tyrosine Protein Kinase ◽  
Substrate Phosphorylation ◽  
High Level

The tyrosine protein kinase activities of pp60c-src and pp60v-src were compared. The activities were qualitatively similar in vitro when the src proteins were bound in an immune complex with monoclonal antibody; both proteins utilized either ATP or GTP as phosphate donors, preferred Mn2+ to Mg2+, and had similar exogenous substrate specificities. The specific activity of pp60c-src was about 10-fold lower than that of pp60v-src for exogenous substrate phosphorylation but was only 1.1- to 2-fold lower than that of pp60v-src for autophosphorylation. Six glycolytic enzymes, including three not previously identified as substrates for pp60src phosphorylation, were phosphorylated by both pp60c-src and pp60v-src. Levels of pp60c-src fourfold higher than the amount of pp60v-src in src-plasmid-transformed cells did not detectably alter the level of phosphotyrosine in cellular proteins, but increasing the expression of pp60c-src another twofold (which induces cells to form foci in monolayer culture (P.J. Johnson, P.M. Coussens, A.V. Danko, and D. Shalloway, Mol. Cell. Biol. 5:1073-1083, 1985) resulted in a threefold increase in the level of cellular protein phosphotyrosine. Immunoprecipitation and analysis of the alkali-stable phosphoproteins by two-dimensional electrophoresis showed that, in contrast to pp60v-src-transformed cells, pp36 and enolase are only weakly phosphorylated in these high-level pp60c-src overexpresser cells. Even allowing for the in vitro differences in specific activities of phosphorylation, these results suggest that the pp60c-src tyrosine protein phosphorylating activity may be restricted relative to that of pp60v-src by additional in vivo mechanisms.

Effect of hyperthermia on the viability and proliferative activity of tumor cells

2016 ◽  
Vol 21 (5) ◽  
pp. 250-252
Author(s):  
N. Yu Anisimova ◽  
M. V Kiselevskiy ◽  
Amir G. Abdullaev ◽  
N. V Malakhova ◽  
S. M Sitdikova ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Physiological Activity ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Transformed Cells ◽  
Cell Mortality ◽  
Temperature Exposure ◽  
The Impact

Introduction. Results of the systemic chemotherapy in the peritoneum canceromatosis are unsatisfactory because of poor penetration of anticancer drugs in serous cavities due to the presence ofperitoneal-plasma barrier. One of the possible ways to enhance the action cytostatic agents is the use of chemotherapy and hyperthermia, which, according to some data, has an own cytotoxic effect. The purpose of the study. The study of the effect ofdifferent modes of hyperthermia on the physiological activity of transplantable lines of tumor and non-transformed cells. Results. Analysis of the impact of hyperthermia on the physiological activity of transplantable lines of tumor and the non-transformed cells in vitro and in vivo studies demonstrated that along with the gain in the level and time of the temperature exposure as the degree of damage as tumor cell mortality rate increases. In this study the most effective treatment was as follows: the temperature is above 45°C with the exposure of more than 2 hours, which is difficult to achieve in practice due to the limited tolerance of healthy tissues. Conclusion. With the use of hyperthermia in monoregimen it is not possible to achieve effective levels of the temperature impact, which could hardly have a significant inhibitory effect on tumor cells.

Infection of mammalian cells with Theileria species

Parasitology ◽  
1983 ◽  
Vol 86 (2) ◽  
pp. 243-254 ◽  
Author(s):  
D. A. Stagg ◽  
A. S. Young ◽  
B. L. Leitch ◽  
J. G. Grootenhuis ◽  
T. T. Dolan
Keyword(s):  
Host Range ◽  
Mammalian Cells ◽  
Mammalian Species ◽  
Rhipicephalus Appendiculatus ◽  
Host Cells ◽  
Transformed Cells ◽  
Theileria Parva ◽  
African Buffalo

SUMMARYExperiments were carried out to determine the susceptibility of mammalian cells to infection with different species of Theileria in vitro. Sporozoites of Theileria parva (parva), Theileria parva (lawrencei) and Theileria taurotragi were isolated from Rhipicephalus appendiculatus ticks by grinding infected ticks in medium, filtering the suspension and concentrating by centrifugation. The sporozoites were used in attempts to infect in vitro peripheral blood leucocytes harvested from 16 different mammalian species which included 12 species of Bovidae from 6 different sub-families. The technique was shown to be both sensitive and reproducible. The sporozoites of T. parva (parva) infected and transformed cells from 2 species of the sub-family Bovinae, the two cattle types and African buffalo. Theileria parva (lawrencei) infected and transformed cells from the two cattle types, African buffalo and Defassa waterbuck. Theileria taurotragi sporozoites infected in vitro cells from 11 different species of Bovidae which were members of 6 sub-families; Bovinae, Tragelaphinae, Reduncinae, Alcelaphinae, Antilopinae and Caprinae. Transformed lymphoblastoid cell lines were established from 7 of the species infected. Sporozoite attachment and infection was not observed with non-susceptible bovid host cells, nor were any of the non-bovid leucocytes infected by the parasites. The host range observed in this study corresponded to the known host range in vivo.

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