scholarly journals Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.

1992 ◽  
Vol 119 (2) ◽  
pp. 427-438 ◽  
Author(s):  
J L Rodríguez Fernández ◽  
B Geiger ◽  
D Salomon ◽  
I Sabanay ◽  
M Zöller ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Suppressive Effect ◽  
Soft Agar ◽  
Transformed Cells ◽  
Tumor Cell Lines ◽  
3T3 Cells ◽  
Apparent Increase ◽  
Cell Matrix ◽  
Endogenous Protein

Transfection of chicken vinculin cDNA into two tumor cell lines expressing diminished levels of the endogenous protein, brought about a drastic suppression of their tumorigenic ability. The SV-40-transformed Balb/c 3T3 line (SVT2) contains four times less vinculin than the parental 3T3 cells, and the rat adenocarcinoma BSp73ASML has no detectable vinculin. Restoration of vinculin in these cells, up to the levels found in 3T3 cells, resulted in an apparent increase in substrate adhesiveness, a decrease in the ability to grow in soft agar, and suppression of their capacity to develop tumors after injection into syngeneic hosts or nude mice. These results suggest that vinculin, a cytoplasmic component of cell-matrix and cell-cell adhesions, may have a major suppressive effect on the transformed phenotype.

Effects of ouabain on NIH/3T3 cells transformed with retrovirai oncogenes and on human tumor cell lines

1987 ◽  
Vol 40 (5) ◽  
pp. 653-658 ◽  
Author(s):  
Pierosandro Tagliaferri ◽  
Kazuyoshi Yanagihara ◽  
Fortunate Ciardiello ◽  
Neil Talbot ◽  
Ursula Flatow ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
3T3 Cells ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals A transforming activity not detected by DNA transfer to NIH 3T3 cells is detected by JB6 mouse epidermal cells.

1985 ◽  
Vol 5 (4) ◽  
pp. 890-893 ◽  
Author(s):  
N H Colburn ◽  
M I Lerman ◽  
G A Hegamyer ◽  
T D Gindhart
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
3T3 Cells ◽  
Anchorage Independence ◽  
Transforming Activity ◽  
Mouse Epidermal Cell ◽  
Nih 3T3 ◽  
Transforming Genes ◽  
Nih 3T3 Cells

Transfection of four different mouse epidermal tumor cell DNAs into NIH 3T3 cells yielded neither morphologically altered foci nor anchorage independence. However, promotion-sensitive, but not promotion-insensitive, JB6 mouse epidermal cell lines were permissive for the expression of anchorage independence after transfection of DNA from three of these tumor cell lines. This transforming activity and the promotion-sensitive activity that confers sensitivity to promotion of transformation show differences in restriction enzyme sensitivity. In view of this difference and the differences in both recipient cells and 12-O-tetradecanoyl-phorbol-13-acetate dependence of expression, it appears that the transforming activity and the promotion-sensitive activity are specified by different genes. The JB6 promotion-sensitive cell lines may be useful for detecting and cloning transforming genes that escape detection in the NIH 3T3 cell focus assay.

scholarly journals Effects of Febrile Temperature on Adenoviral Infection and Replication: Implications for Viral Therapy of Cancer

2005 ◽  
Vol 79 (1) ◽  
pp. 581-591 ◽  
Author(s):  
Stephen H. Thorne ◽  
Gabriel Brooks ◽  
Yeun-Ling Lee ◽  
Tina Au ◽  
Lawrence F. Eng ◽  
...  
Keyword(s):  
Viral Replication ◽  
Tumor Cell ◽  
Cell Lines ◽  
Therapeutic Index ◽  
Oncolytic Viruses ◽  
Transformed Cells ◽  
Hsp70 Expression ◽  
Tumor Cell Lines ◽  
Adenoviral Infection ◽  
Transformed Cell Lines

ABSTRACT We previously conducted a phase I/II study using arterial infusions of ONYX-015 (dl1520), a replication-selective adenoviral vector, with E1b deleted, for patients with metastatic colorectal cancer. No dose-limiting toxicities occurred, but >90% of the patients experienced fever. The effects of temperature on the replication of dl1520 in normal and transformed cells had not been studied. Therefore, replication and cell viability assays were performed with a panel of nontransformed and transformed cell lines cultured at 37 and 39.5°C and treated with adenovirus type 5 (Ad5) or dl1520. Ad5-mediated cytolytic effects were inhibited and production of infectious particles decreased by >1,000-fold in the nontransformed cells at 39.5°C. Seven of nine of the tumor cell lines retained significant cell-killing effects when treated with Ad5 at 39.5°C. When dl1520 was used, no cytolytic effects were observed at 39.5°C in the nontransformed cell lines; however, cytolytic effects occurred in six of nine tumor cell lines at 39.5°C. Notably, a subset of the tumor cell lines demonstrated increased dl1520-mediated cytolytic effect and replication at 39.5°C. Suppression of Ad5 and dl1520 replication at 39.5°C was not related to p53 status or HSP70 expression. Also, at 39.5°C, E1a expression was inhibited in nontransformed cells but was still abundant in the transformed cells, indicating that a novel early block in viral replication occurred in the nontransformed cells. Fever may therefore augment the therapeutic index of oncolytic viruses by inhibiting replication in normal cells while permitting or enhancing viral replication in some tumor cells.

scholarly journals Constitutive phosphorylation of eps8 in tumor cell lines: relevance to malignant transformation.

1995 ◽  
Vol 15 (7) ◽  
pp. 3805-3812 ◽  
Author(s):  
B Matoskova ◽  
W T Wong ◽  
A E Salcini ◽  
P G Pelicci ◽  
P P Di Fiore
Keyword(s):  
Tumor Cell ◽  
Tyrosine Phosphorylation ◽  
Cell Lines ◽  
Egf Receptor ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

eps8, a recently identified tyrosine kinase substrate, has been shown to augment epidermal growth factor (EGF) responsiveness, implicating it in EGF receptor (EGFR)-mediated mitogenic signaling. We investigated the status of eps8 phosphorylation in normal and transformed cells and the role of eps8 in transformation. In NIH 3T3 cells overexpressing EGFR (NIH-EGFR), eps8 becomes rapidly phosphorylated upon EGF stimulation. At receptor-saturating doses of EGF, approximately 30% of the eps8 pool is tyrosine phosphorylated. Under physiological conditions of activation (i.e., at low receptor occupancy), corresponding to the 50% effective dose of EGF for mitogenesis, approximately 3 to 4% of the eps8 contains phosphotyrosine. In human tumor cell lines, we detected constitutive tyrosine phosphorylation of eps8, with a stoichiometry (approximately 5%) similar to that associated with potent mitogenic response in NIH-EGFR cells. Overexpression of eps8 was able to transform NIH 3T3 cells under limiting conditions of activation of the EGFR pathway. Concomitant tyrosine phosphorylation of eps8 and shc, but not of rasGAP, phospholipase C-gamma, and eps15, was frequently detected in tumor cells. This suggested that eps8 and shc might be part of a pathway which is preferentially selected in some tumors. Cooperation between these two transducers was further indicated by the finding of their in vivo association. This association was, at least in part, dependent on recognition of shc by the SH3 domain of eps8. Our results indicate that eps8 is physiologically part of the EGFR-activated signaling and that its alterations can contribute to the malignant phenotype.

scholarly journals p53-Independent Endoplasmic Reticulum Stress-Mediated Cytotoxicity of a Newcastle Disease Virus Strain in Tumor Cell Lines

2007 ◽  
Vol 81 (6) ◽  
pp. 2817-2830 ◽  
Author(s):  
Zsolt Fábián ◽  
Christine M. Csatary ◽  
József Szeberényi ◽  
Laszlo K. Csatary
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Tumor Cell ◽  
Newcastle Disease Virus ◽  
Cell Lines ◽  
Newcastle Disease ◽  
Apoptotic Cell ◽  
Transformed Cells ◽  
Tumor Cell Lines

ABSTRACT While Newcastle disease virus (NDV) causes serious infections in birds, it is apparently nonpathogenic in mammalian species, including humans. Previous observations and small-scale clinical trials indicated that NDV exerts oncolytic effects. Isolates of NDV were found to have selective affinity to transformed cells. We previously showed that the attenuated NDV strain MTH-68/H causes apoptotic cell death in cultures of PC12 rat pheochromocytoma cells. The aim of the present study was to extend MTH-68/H cytotoxicity testing with human tumor cell lines and to analyze certain biochemical aspects of its oncolytic effect. MTH-68/H was found to be able to kill a wide range of transformed cells by apoptosis. While caspase-8 and caspase-9 are not involved in MTH-68/H-induced apoptosis, activation of caspase-3 and caspase-12 was detected in virus-infected PC12 cells. A human glioblastoma cell line with repressible expression of the p53 protein did not show any difference in MTH-68/H sensitivity in its p53-expressing and p53-depleted states, indicating that the apoptotic process induced by MTH-68/H does not depend on p53. Apoptosis was accompanied by virus replication in two tumor cell lines tested (PC12 cells and HeLa human cervical cells), and signs of endoplasmic reticulum stress (phosphorylation of protein kinase R-like endoplasmic reticulum kinase and eIF2α) were also detected in transformed cells. In contrast, proliferation of nontransformed mouse and rat fibroblast cell lines and human primary fibroblasts was not affected by MTH-68/H treatment. MTH-68/H thus selectively kills tumor cell cultures by inducing endoplasmic reticulum stress leading to p53-independent apoptotic cell death.

scholarly journals Analysis of Human Ascites Effect on Clonogenic Growth of Human Tumor Cell Lines and NRK-49F Cells in Soft Agar

1987 ◽  
Vol 5 (2) ◽  
pp. 158-169 ◽  
Author(s):  
H. J. Broxterman ◽  
C Sprenkels-Schotte ◽  
A. Leyva ◽  
H. M. Pinedo ◽  
P. H. Engelen
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Soft Agar ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Clonogenic Growth

A transforming activity not detected by DNA transfer to NIH 3T3 cells is detected by JB6 mouse epidermal cells

1985 ◽  
Vol 5 (4) ◽  
pp. 890-893
Author(s):  
N H Colburn ◽  
M I Lerman ◽  
G A Hegamyer ◽  
T D Gindhart
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
3T3 Cells ◽  
Anchorage Independence ◽  
Transforming Activity ◽  
Mouse Epidermal Cell ◽  
Nih 3T3 ◽  
Transforming Genes ◽  
Nih 3T3 Cells

Transfection of four different mouse epidermal tumor cell DNAs into NIH 3T3 cells yielded neither morphologically altered foci nor anchorage independence. However, promotion-sensitive, but not promotion-insensitive, JB6 mouse epidermal cell lines were permissive for the expression of anchorage independence after transfection of DNA from three of these tumor cell lines. This transforming activity and the promotion-sensitive activity that confers sensitivity to promotion of transformation show differences in restriction enzyme sensitivity. In view of this difference and the differences in both recipient cells and 12-O-tetradecanoyl-phorbol-13-acetate dependence of expression, it appears that the transforming activity and the promotion-sensitive activity are specified by different genes. The JB6 promotion-sensitive cell lines may be useful for detecting and cloning transforming genes that escape detection in the NIH 3T3 cell focus assay.

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