Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transformers”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed1984

Behavior of transforming growth factors in serum-free media: an improved assay for transforming growth factors.

Transforming growth factors (TGFs) are a relatively new category of factors that induce the anchorage-independent growth of non-transformed cells. These factors are usually detected by their ability to induce normal rat kidney (NRK) fibroblasts to grow in soft agar. Until now, this assay has been performed in serum-containing medium (SCM). Unfortunately, the background activity of this assay is variable and dependent on several factors, including passage number of the cells and the serum lot used. Furthermore, the addition of either EGF or TGF-beta alone results in the appearance of additional colonies, which decreases the sensitivity of the assay. To circumvent these problems, serum-free media have been developed that support the growth of the NRK cells at low density in both monolayer culture and soft agar. Long-term growth in monolayer cultures occurs in serum-free medium supplemented with laminin, insulin, transferrin, epidermal growth factor (EGF), fibroblast growth factor (FGF) and high density lipoprotein (HDL). Growth in soft agar occurs when TGFs are added to a serum-free medium, AIG medium, that contains insulin, transferrin, FGF and HDL. In contrast to the background activity observed when the assay is performed in SCM, no colonies form in the AIG medium unless TGFs are added and few, if any, colonies form if EGF or TGF-beta are added alone. Thus, the AIG medium provides an improved assay for TGFs. In addition, the AIG medium should prove useful for examining other factors, including serum factors, for TGF activity.

Animals↗
PubMed1998

Karyotypic changes associated with spontaneous acquisition and loss of tumorigenicity in a human transformed bronchial epithelial cell line: evidence for in vivo selection of transformed clones.

In this study, we describe the karyotypic changes associated with the spontaneous acquisition of tumorigenicity in an immortalized tumor bronchial cell line. Neoplastic transformation of the NL20 human bronchial epithelial cell line occurred after 3 yr in culture, and was associated with loss of chromosome 18 together with acquisition of multiple copies of 9q21.2-->34. The nontumorigenic NL20 cell line had been established by transfection of human bronchial epithelial cells with the SV40 T antigen, and had retained a relatively stable karyotype after the first 32 passages in vitro. However, when cells from p184 were inoculated into nude mice, a transplantable tumor was obtained that was derived from a minor clone present in this otherwise stable line. Subsequent passaging of the NL20 cells in vitro did not yield further tumors, and the minor clone from which the tumorigenic NL20T cell line derived was no longer evident in NL20 cells by Passage 205. Furthermore, the original tumorigenic NL20T cells lost the neoplastic phenotype after 25 passages in vitro and reverted to the nontumorigenic karyotype observed at p189. In contrast to the loss of the tumorigenic phenotype and karyotype, which occurred with in vitro passaging of the original tumor, when the NL20T cells were passaged in other nude mice, they continued to give rise to tumors with sevenfold amplifications of 9q sequences and loss of chromosome 18, and cells from the secondary tumors (NL20T-A cells) have maintained a stable karyotype and remain tumorigenic even after 64 passages in vitro. A mixture of 10% tumorigenic NL20T-A and 90% nontumorigenic NL20 cells formed tumors in athymic nude mice when cultured in vitro on fibronectin, but not on plastic; cytogenetic analysis demonstrated that the tumors and cell cultures were composed of tumorigenic NL20T-A cells, whereas cytogenetic analysis of cells cultured on plastic were identical to the nontumorigenic NL20 cells. These data support the hypothesis that neoplastic transformation in our original cell line arose from in vivo selection of a small mutant clone, which had arisen in culture and was subsequently selected in vivo but was lost with in vitro culture.

Animals↗
PubMed1987

Effects of substituted 2-nitroimidazoles and related compounds on unscheduled DNA synthesis in rat hepatocytes and in non-transformed (BL8) and transformed (JB1) rat liver epithelial derived cell lines.

1. Using unscheduled DNA synthesis as an index, the possible interaction of a number of substituted nitroimidazoles, e.g. misonidazole, with cellular DNA has been investigated. Transformed (JB1), non-transformed (BL8) rat liver epithelial derived cell lines and freshly prepared rat hepatocytes have been used. 2. Under anaerobic or aerobic conditions, relative to cells exposed to a nitroquinoline-N-oxide standard, misonidazole and related nitroimidazoles were very poor at stimulating unscheduled DNA synthesis in JB1 or BL8 cells or in hepatocytes, even at the highest concentrations tested (10 mM). Under anaerobic conditions, metabolic activation did occur as judged from the time-dependent depletion of cellular reduced glutathione in all three cell types. 3. It was concluded that in hypoxic cells an important mode of action of such nitroimidazoles as chemotherapeutic sensitisers may be by their interaction with cellular thiols rather from their interaction with DNA. 4. Functionalisation of the nitroimidazole ring with a side chain containing an aziridine function, e.g. RSU-1069 (1-(2-nitro-1-imidazolyl)-3-(1-aziridinyl)-2-propanol), results in the induction of unscheduled DNA synthesis in cells exposed under both aerobic and anaerobic conditions. On a molar basis, however, this induction was not so great as that caused by the simple monofunctional alkylating agent 1-aziridineethanol itself. Methyl-substitution of the aziridine ring in RSU-1069 reduced the extent of unscheduled DNA synthesis. 5. With all the compounds tested, unscheduled DNA synthesis was greater in JB1 cells than in BL8s or in hepatocytes.

Animals↗
PubMed1983

Expression of integrated viral DNA sequences outside the transforming region in eight adenovirus-transformed cell lines.

The expression of early and intermediate-early viral regions in eight adenovirus type 5 transformed cell lines was analyzed by radioimmuno-inhibition and RNA-DNA hybridization techniques. Details on the arrangement of the integrated viral DNA sequences in these cell lines have already been published (Visser, L., Wassenaar, A.D.C., Van Maarschalkerweerd, M.W. and Rozijn, T.H. (1981) J. Virol, 39, 684-693). In all cell lines tested, proteins encoded by the transforming region E1 are present. Dependent on the viral DNA content, additional early regions are expressed in most cell lines. In two of the cell lines polypeptides related to the adenoviral terminal protein, encoded by the recently described region E2b, could be detected. The viral DNA sequence encoding the body of the terminal protein mRNA is probably integrated intact, but the promoter region and at least some of the leaders are lacking in these cell lines.

Adenoviruses, Human↗
PubMed1991

A comparison of transcriptional regulatory element activities in transformed and non-transformed rat anterior pituitary cells.

Transformed (GH-3) and non-transformed (P3) rat anterior pituitary cells were compared in their ability to direct expression of plasmids containing a variety of eukaryotic transcriptional regulatory elements (TREs). These include the herpes simplex virus thymidine kinase (HSV-TK), Rous sarcoma virus long terminal repeat (RSV-LTR), simian virus 40 early (SV-40E), human cytomegalovirus immediate-early (CMV-IE) and mouse metallothionein 1 (mMT-1) TREs. Chloramphenicol acetyl transferase (CAT) gene expression served as a reporter in this study. Following transient transfection, the cell lines exhibited similar profiles of TRE utilization. In each cell line. CMV-IE was most efficient in directing reporter gene expression, although 2-fold greater activity was observed in GH-3 versus P3 cells. RSV-LTR directed gene expression was lower than that of CMV-IE while both HSV-TK and SV-40E were inactive in each cell line. Also, the mMT-1 promoter was inducible by addition of ZnCl2 to the culture media, though the level required for maximal activation differed between the two cell lines. Transfected GH-3 and P3 cells, therefore, displayed similar TRE utilization profiles yet significant differences were observed in the ability of these cell lines to respond to specific regulatory elements.

Animals↗
PubMed1995

Incorporation of arachidonic and eicosapentaenoic acids into phospholipids of non-transformed and spontaneously-transformed rat liver epithelial cells: effects on DNA-synthesis.

We compared the incorporation of arachidonic acid (AA) and eicosapentaneoic acid (EPA) into phospholipids of non-transformed (NT-) and spontaneously-transformed (T-) rat liver epithelial cells (RLEC), and their consequences on DNA-synthesis. In NT-cells, both radioactive fatty acids were preferentially incorporated into phosphatidylcholine (PC). In T-cells, in contrast, AA was predominantly incorporated into phosphatidylethanolamine (PE), whereas EPA remained preferentially incorporated into PC. After pulse labelling, we observed in both cell types a progressive decrease in AA- and EPA-labelled PC associated with an increase in AA- and EPA-labelled PE. Preincubation of NT-cells with increasing concentrations of AA or EPA (0.1 microM to 20 microM) resulted in a concentration-dependent DNA-synthesis stimulation with a stronger effect of AA compared with EPA. In T-cells, the same treatment had no effect on DNA-synthesis.

Animals↗
PubMed2005

Milk growth factor (MGF) induces transformation into ATDC5 cells, prechondrocytes, and cooperates with retinoic acid to transform the cells into new forms.

The effects of milk growth factor (MGF) showed the transformation of ATDC5 prechondrocytes and differed from that of retinoic acid (RA) as follows. MGF (200 ng/ml) did not suppress the proliferation of ATDC5 cells, though RA (1 x 10(-7) M) suppressed the cell proliferation. However, MGF showed the result as RA, which was verified to suppress the production of proteoglycan. The synthesis of vimentin in ATDC5 cells was slightly induced by RA, but its withdrawal induced the large-scale induction and the fibril formation of vimentin, which may indicate that the cells became fibroblastic cells, namely dedifferentiation. MGF, which hardly induced the vimentin synthesis in ATDC5 cells, induced its synthesis under control by the withdrawal. MGF suppressed the synthesis of alpha-smooth muscle actin (alpha-SM-actin), which was apt to reverse in its withdrawal. However, RA did not affect this synthesis of ATDC5 cells. The combination of MGF and RA enlarged the cells and enhanced the synthesis of vimentin due to RA under control, however, almost terminated alpha-SM-actin-synthesis in the cells. And its effect is almost irreversible. Furthermore, the combination of MGF and RA prevented the induction of fibroblasts due to RA in the cells. And the withdrawal of the mixture transformed prechondrocytes into hypertrophic cells. Then, MGF contributes to bone metabolism in prechondrocyte.

Actins↗
PubMed1995

Muscle fibre expression of transforming growth factor-beta 1 and latent transforming growth factor-beta binding protein in canine masticatory muscle myositis.

Masticatory muscle myositis (MMM) is presumed to be an immunologically mediated canine myopathy but is of unknown origin. Severe atrophy and degeneration of masticatory muscle fibres, infiltration of eosinophilic granulocytes, and proliferation of the fibrous interstitial tissue are the hallmarks of MMM. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory peptide controlling myogenesis, inflammation and tissue repair. We investigated immunocytochemically the expression of TGF-beta 1 and latent transforming growth factor-beta binding protein (LTBP), a TGF-beta modulator protein, in cases of MMM. The study demonstrated the presence of TGF-beta and LTBP in muscle fibres. infiltrating leucocytes and extracellular matrix in MMM, and suggested that TGF-beta and LTBP play a role in muscle tissue repair, inflammation and fibrogenesis in MMM.

Animals↗
PubMed2002

The origin of transformed cells. studies of spontaneous and induced cell transformation in cell cultures from marsupials, a snail, and human amniocytes.

Transformation of cells in culture is a model system for carcinogenesis, and two major theories (i.e., mutagenesis and aneuploidy) have emerged from in vitro and in vivo studies. A third view is presented here on the initial steps in the change of primary cells to extended life cells, and their change to immortalized cells. Both changes involve identical, microscopically visible cell abnormalities hitherto dismissed as cell degenerative characteristics. The major cell changes (i.e., giant cells, nuclear fragmentation to form multinucleated cells [MNC]) translated into genetic terms begin with the creation of polyploidy by DNA endoreduplication, followed by amitotic division of these giant cells to produce MNC. Individual nuclei, surrounded by a cell membrane, bud from the surface of the MNC, and represent the origin of the transformed cells. Induced budding by a protease treatment of MNC suggests that the extracellular matrix is an inhibitor of the budding process from human MNC. The production of the MNC is a genetic process determined by two abnormal events (i.e., overproduction of DNA and amitotic chromosomal segregation) during which there are possibilities for different genetic mechanisms to produce inherited variability within and between MNC. These concepts are discussed in regard to carcinogenesis, and by extension its possible prevention by use of the special cytopathic cell changes in carcinogen testing and in clinical screening programs.

Animals↗
PubMed2003

Comparison of the cytotoxicity of two nitroheterocyclic drugs (NHCD) towards transformed and non-transformed cells.

The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3'3'-dimethylaminopropylamino) acridine (Polfa, Poland) and Quinifuryl, 2-(5'-nitro-2'-furanyl) ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline (Dr. N. M. Sukhova, Institute of Organic Synthesis, Riga, Latvian Republic), towards two lines of leukaemic cells and a line of non-transformed cells, was determined under normoxia conditions. Although both drugs showed significant cytotoxicity to all cell lines (LC(50) for 24h, < or = 2 microM) with that of Nitracrine exceeding Quinifuryl, their toxicity towards murine leukaemia P388 was substantially higher, compared to murine fibroblasts NIH3T3. In addition, the rate of cell death was also two- to three-fold higher in case of P388 cells versus NIH3T3. Interestingly, human erythroleukaemia K562 cells were shown to uptake the drugs 10 min after their addition to the tissue culture medium, while the LC(50) values were reached after a substantial delay of 3h. This delay might be due to the intracellular transformation of drugs required for cell killing.

Animals↗
PubMed2003

Effect of the dithiocarbamate pesticide zineb and its commercial formulation, the azzurro. V. Abnormalities induced in the spindle apparatus of transformed and non-transformed mammalian cell lines.

Abnormalities induced in the mitotic spindle by zineb and azzurro (1.0-25.0 micro g/ml, 24h) were evaluated in Chinese hamster ovary (CHO) and HeLa cells, and in non-transformed human fibroblasts (NTHF). Spindles were stained with FITC-conjugated anti-beta tubulin. Treatment with 10.0 micro g/ml of zineb induced complete inhibition of cell viability in NTHF cells while 10.0 micro g/ml of azzurro decreased cell growth down to 62%. Higher doses of both compounds induced cell death. In HeLa and CHO cells, 15.0 micro g/ml of zineb and 10.0-15.0 micro g/ml of azzurro decreased viability, whereas 25.0 micro g/ml of both compounds was cytotoxic. A significantly decreased mitotic index (MI) was observed in NTHF treated with 5.0 micro g/ml zineb or azzurro, whereas 10.0 micro g/ml of both chemicals were necessary to induce the same phenomenon in HeLa and CHO cells. Treatment with 1.0-5.0 micro g/ml of zineb or azzurro induced a dose-dependent increase of degenerated spindles in NTHF and the number of degenerated or multipolar spindles in HeLa and CHO cells increased in a dose-dependent manner with 1.0-10.0 micro g/ml zineb and azzurro. Although zineb and azzurro were able to induce mitotic spindle abnormalities in all cell types, non-transformed cells were less resistant than immortalized cells.

Animals↗
PubMed1978

Cellular transformation and the 'morphologic phenotype' of transformed cells.

Expression of the product of the transforming gene (src) of RNA tumour viruses promotes growth and usually alters the adhesion, appearance and surface properties of cultured fibroblasts. The latter group of properties termed the 'morphologic phenotype' of transformed cells is largely due to diminished cell-to-substratum adhesion. The role of cyclic AMP, cell surface protein (CSP), and other factors in producing the 'morphologic phenotype' are discussed. The effects of src expression bear a striking resemblance to the action of peptide hormones such as insulin on appropriate target cells.

Animals↗
PubMedDate not supplied

Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells.

The partial amino-acid sequence of purified human transforming growth factor-beta (TGF-beta) was used to identify a series of cDNA clones encoding the protein. The cDNA sequence indicates that the 112-amino acid monomeric form of the natural TGF-beta homodimer is derived proteolytically from a much longer precursor polypeptide which may be secreted. TGF-beta messenger RNA is synthesized in various normal and transformed cells.

Amino Acid Sequence↗
PubMed1996

Expression of hepatocyte growth factor, transforming growth factor alpha, and transforming growth factor beta 1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation.

Hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF-alpha) stimulate liver regeneration, whereas transforming growth factor beta 1 (TGF-beta 1) inhibits it in rats. However their significance in human liver diseases, especially in severe acute liver injury, remains unclear. We studied HGF, TGF-alpha, and TGF-beta 1 messenger RNA (mRNA) expression in the livers of patients with live diseases using a competitive reverse transcriptase polymerase chain reaction. As little as a twofold difference in mRNA expression could be detected from minute liver biopsy samples. We then examined cell proliferation using proliferating cell nuclear antigen (PCNA) staining. HGF mRNA levels were significantly higher (approximately threefold) in acute hepatitis (AH) than in exacerbation of chronic liver disease (EX) (P < .05). TGF-alpha mRNA levels were significantly greater in AH (approximately twofold) than EX (P < .05), and the levels were significantly higher (approximately threefold) in chronic hepatitis (CH) than in EX (P < .05). The TGF-beta 1 mRNA levels in all the groups were not significantly different. In acute liver injury (AH and EX), there was a significant correlation between HGF mRNA expression and the PCNA labeling index (LI) in the liver (r = .87, P < .005). TGF-alpha mRNA expression also correlated with the PCNA LI (r = .92,P < .0001). There was no significant correlation between the serum HGF and the PCNA LI in the liver. In conclusion, HGF and TGF-alpha produced in the liver stimulate hepatocyte proliferation in response to acute liver injury in humans.

Base Sequence↗
PubMed1969

Gangliosides in DNA virus-transformed and spontaneously transformed tumorigenic mouse cell lines.

In mouse cell lines transformed by SV40 virus, a decrease was observed in the higher ganglioside homologues disialo-ceramidetetrahexoside and monosialo-ceramidetetrahexoside. Such change was observed only in cells which carry the virus genome, and it correlated with increased saturation density in tissue culture and with rejection in immunologically competent syngeneic host. This indicates that the change is one of the virus-regulated functions, and it is postulated that it relates to the rejection of the virus-transformed cells.

Animals↗
PubMed1974

Viral DNA in transformed cells. III. The amounts of different regions of the SV40 genome present in a line of transformed mouse cells.

(32)P-Labeled SV40 DNA was treated sequentially with restricting endonucleases EcoRI and Hpa I, and the resulting four fragments of DNA were separated by gel electrophoresis. The kinetics of renaturation of each of the fragments and of complete SV40 DNA were measured in the presence of DNA extracted from the SVT2 line of SV40-transformed mouse cells. It was found that these cells contain about six copies of a segment of DNA which includes the early region of the SV40 genome, and about one copy of the late viral sequences. To map the region of the viral genome which is transcribed in SVT2 cells, separated strands of each of the four fragments were prepared and hybridized to total transformed cell RNA. Part of the E strands of the two DNA fragments (A and C) which span the early region of the SV40 genome were found to enter the hybrid.

Animals↗
PubMed1982

Fragments of the simian virus 40 transforming gene facilitate transformation of rat embryo cells.

Segments of the simian virus 40 (SV40) genome that encode only fragments of large tumor antigen can facilitate immortalization of secondary rat embryo cells. The phenotypes of the immortalized cells range from nearly "normal" to fully transformed. All of the cell lines contain SV40 sequences and express unstable NH2-terminal fragments of large tumor antigen. SV40 small tumor antigen does not appear to be essential for either immortalization or transformation.

Animals↗