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 307 records · Page 17Linked to original sources
PubMed1995

Differential dependence of the tumorigenicity of chemically transformed rat liver epithelial cells on autocrine production of transforming growth factor alpha.

The tumorigenic phenotype in rat liver epithelial cells overexpressing c-myc may depend on a transforming growth factor (TGF)-alpha/epidermal growth factor receptor autocrine loop (L. W. Lee et al., Cancer Res., 51: 5238-5244, 1991). In the present study, we have used constitutive sense and antisense TGF-alpha expression vectors to modify TGF-alpha production in carcinogen-transformed clonal derivatives of a rat liver epithelial cell line, WB-F344, that variably express c-myc, endogenous TGF-alpha, and tumorigenicity. Transgene-mediated TGF-alpha protein production was elevated 2- to 9-fold in derivatives of a low c-myc-expressing transformed cell line, GN4, and 35-fold in a derivative of a high c-myc-expressing cell line, GN6. Although the GN4- and GN6-derived cell lines expressed functional EGF receptor and steady-state c-myc mRNA levels that were comparable to their respective parental cell lines, increased TGF-alpha expression did not increase the tumorigenicity of the derivatives relative to the parental cell lines. Similarly, in vitro growth characteristics of the GN4- and GN6-derived cell lines were not markedly altered by increased autocrine TGF-alpha production. Additionally, GN4, GN6, and their derivatives were, for the most part, unresponsive to exogenously applied TGF-alpha in vitro. In contrast, antisense TGF-alpha RNA expression significantly suppressed endogenous TGF-alpha production in a high c-myc-expressing, high TGF-alpha-expressing, highly tumorigenic clonal line, GP9; this suppression resulted in lowered steady-state c-myc levels and attenuated in vitro growth. Antisense-mediated suppression of all of these in vitro phenotypes in GP9 was reversed by exogenous TGF-alpha. The latency of tumor formation by the antisense derivative of cell line GP9 was significantly lengthened (> 3-fold) relative to the time required for tumor formation by its parental cell line. These results demonstrate that a TGF-alpha/epidermal growth factor receptor autocrine loop may be necessary for exaggerated in vitro and in vivo growth of some transformed rat liver epithelial cells (e.g., GP9); however, the autocrine loop is not generally sufficient to support tumorigenicity, even in transformed clonal lines expressing elevated levels of c-myc.

Actins↗
PubMed1994

Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium.

Intestinal epithelial cells rest on a fibroblast sheath. Thus, factors produced by these fibroblasts may influence epithelial function in a paracrine fashion. We examined modulation of intestinal epithelial function by one such fibroblast product, scatter factor/hepatocyte growth factor (HGF/SF). This effect was studied in vitro by using model T84 intestinal epithelial cells. When applied to confluent T84 monolayers, HGF/SF attenuates transepithelial resistance to passive ion flow in a dose-dependent manner (maximum fall at 300 ng/ml, 28% control monolayer resistance, P < 0.001, ED50 of 1.2 nM), t1/2 of 20 h. This functional effect of HGF/SF and distribution of its receptor, c-met, are polarized to the basolateral membranes of T84 intestinal epithelial cells. HGF/SF effects on resistance are not attributable to altered transcellular resistance (opening of Cl- and/or basolateral K+ channels), cytotoxicity, or enhanced cell proliferation; they therefore represent specific regulation of paracellular tight junction resistance. Analysis with biochemically purified rodent HGF/SF and Madin-Darby canine kidney cells reveals that effects on paracellular tight junctions also occur in other nontransformed epithelia. Binding of HGF/SF to its receptor in T84 intestinal epithelial cells is accompanied by tyrosine phosphorylation of the receptor. Because loosening of intercellular junctions between cells could facilitate separation, spreading, and migration of epithelial cells during physiologic processes such as wound resealing, we determined the effects of HGF/SF on intestinal epithelial wound resealing using our previously published in vitro model (Nusrat, A., C. Delp, and J. L. Madara. 1992. J. Clin. Invest. 89:1501-1511). HGF/SF markedly enhanced wound closure (> 450% increase in rate, P < 0.001) by influencing the migratory and spreading response in not only cells adjoining the wound but also cells many positions removed from the wound. We thus speculate that HGF/SF may serve as an important cytokine that influences epithelial parameters such as transepithelial resistance and wound resealing. Further pharmacological approaches to manipulate HGF/SF signaling pathways may provide novel therapeutic strategies to enhance repair of intestinal epithelial erosions/ulcerations.

Animals↗
PubMed2004

Transformation of ginseng saponins to ginsenoside Rh2 by acids and human intestinal bacteria and biological activities of their transformants.

When ginseng water extract was incubated at 60 degrees C in acidic conditions, its protopanaxadiol ginsenosides were transformed to ginsenoside Rg3 and delta20-ginsenoside Rg3. However, protopanaxadiol glycoside ginsenosides Rb1, Rb2 and Rc isolated from ginseng were mostly not transformed to ginsenoside Rg3 by the incubation in neutral condition. The transformation of these ginsenosides to ginsenoside Rg3 and delta20-ginsenoside Rg3 was increased by increasing incubation temperature and time in acidic condition: the optimal incubation time and temperature for this transformation was 5 h and 60 degrees C resepectively. The transformed ginsenoside Rg3 and delta20-ginsenoside Rg3 were metabolized to ginsenoside Rh2 and delta20-ginsenoside Rh2, respectively, by human fecal microflora. Among the bacteria isolated from human fecal microflora, Bacteroides sp., Bifidobacterium sp. and Fusobacterium sp. potently transformed ginsenoside Rg3 to ginsenoside Rh2. Acid-treated ginseng (AG) extract, fermented AG extract, ginsenoside Rh2 and protopanaxadiol showed potent cytotoxicity against tumor cell lines. AG extract, fermented AG extract and protopanaxadiol potently inhibited the growth of Helicobacter pylori.

Animals↗
PubMed2006

Optimization of wheat co-transformation procedure with gene cassettes resulted in an improvement in transformation frequency.

Genetic manipulation using gene cassettes was applied to the elite wheat variety EM12 via particle bombardment, which allows an improvement in transformation frequency. We simultaneously transferred to wheat immature embryos with two non-linked genes, gus and bar, on either separate gene cassettes or one plasmid. The linear gene cassettes were excised and purified by restriction digestion of the plasmid, and consisted of promoters, open reading frames and terminators. No difference was observed in GUS transient expression of between gene cassettes and single whole plasmid. However, the stable transformation frequency was significantly increased to 1.1% using gene cassettes, compared with 0.4% when using single plasmid. Procedures of the efficient co-transformation with gene cassettes were developed. Factors influencing on the transformation frequency were also studied in order to optimize the procedure. These were acceleration pressure, target distance, gold particle size, the quantity ratio of gene cassettes and the age of target explants. Based on the transient and stable expression of the gus gene cassettes, optimization of transformation parameters improved the reproducibility of transformation in the elite wheat variety.

Gene Expression Regulation, Plant↗
PubMed1989

Microbial transformation of steroids--II. Transformations of progesterone, testosterone and androstenedione by Phycomyces blakesleeanus.

Phycomyces blakesleeanus transformed progesterone, testosterone and androstenedione into mixtures of products. Five monohydroxylated metabolites were obtained in reasonable yields from the progesterone transformation. Only 7 alpha- and 15 beta-hydroxyprogesterone have been reported previously from this organism. We find that it gives these two metabolites and also 6 beta-, 14 alpha- and 15 alpha-hydroxyprogesterone as major products. Five compounds were also purified from testosterone transformation mixtures. Two of these were monohydroxylated, two were ring A dehydrogenation products, and two were oxidised at C-17. The products were identified as 6 beta-hydroxytestosterone, 7 alpha-hydroxytestosterone, androsta-1,4-diene-3,17-dione (1-dehydroandrostenedione), 17 beta-hydroxyandrosta-1,4-diene-3-one (1-dehydrotestosterone) and androstenedione. All five metabolites were produced in reasonable yields, although hydroxylation was the minor transformation in this case. Only two significant products were formed from androstenedione. Both were reduced at C-17; one was also monohydroxylated. They were testosterone and 14 alpha-hydroxytestosterone. The testosterone and androstenedione transformation products have not been reported previously for this organism. We also report for the first time the preparation of P. blakesleeanus cell-free extracts which transformed progesterone reasonably efficiently and faithfully in vitro, although the proportions of each product varied from one extract to another.

Androstadienes↗
PubMed1995

Compound mutants for the paralogous hoxa-4, hoxb-4, and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed.

The Hox gene products are transcription factors involved in specifying regional identity along the anteroposterior body axis. In the mouse, several single mutants for Hox genes show variably penetrant, partial homeotic transformations of vertebrae at their anterior limits of expression, suggesting that compound Hox mutants might show more complete transformations with greater penetrance than the single Hox mutants. Compound mutants for the paralogous group 3 genes, hoxa-3 and hoxd-3, show deletion of a cervical vertebrae, which is not readily interpretable in terms of an alteration in regional identity. Here, we report the skeletal phenotypes of compound mutants in the group 4 Hox genes, hoxa-4, hoxb-4, and hoxd-4. Mice mutant for each of these genes were intercrossed to generate the three possible double mutant combinations and the triple mutant. In contrast to the hoxa-3, hoxd-3 double mutants, group 4 Hox compound mutants displayed clear alterations in regional identity, including a nearly complete transformation of the second cervical vertebrae toward the morphology of the first cervical vertebra in one double mutant combination. In comparing the types of homeotic transformations observed, different double mutant combinations showed different degrees of synergism. These results suggest a certain degree of functional redundancy among paralogous genes in specifying regional identity. Furthermore, there was a remarkable dose-dependent increase in the number of vertebrae transformed to a first cervical vertebra identity, including the second through the fifth cervical vertebrae in the triple mutant. Thus, these genes are required in a larger anteroposterior domain than is revealed by the single mutant phenotypes alone, such that multiple mutations in these genes result in transformations of vertebrae that are not at their anterior limit of expression.

Animals↗
PubMed1996

Statistical analysis of blood- to breath-alcohol ratio data in the logarithm-transformed and non-transformed modes.

The statistical analysis of non-transformed and logarithm-transformed blood- to breath-alcohol ratios ("blood/breath ratios") is detailed. The data analyzed were derived from 137 simultaneous blood-alcohol and breath-alcohol concentration measurements made between 15 and 179 min after the end of drinking, with 136 of the measurements obtained during the 15- to 124-min time frame. Although the distribution of the non-transformed ratios is positively skewed, and that of the logarithm-transformed data more closely approximates the normal distribution upon visual inspection, both analyses generated results that do not differ significantly from each other when considered in the context of "mean ratios + or - 2SD". This is in accord with the results of the Kolmogorov-Smirnov goodness-of-fit test, which does not reject either dataset and demonstrates that both are approximately normal. Since the logarithm-transformed data generate more conservative statistical blood/breath ratio ranges than the non-transformed data, they were selected as the basis for the principal conclusion of this work. That conclusion is a refutation of the argument that, breath-alcohol analyzers relying on a 2100:1 blood/breath ratio tend to underestimate the blood-alcohol concentrations of driving-while-intoxicated arrestees because the commonly accepted mean postabsorptive ratio is 2300:1. In fact, whenever the absorption status of a driving-while-intoxicated arrestee at the time of a breath test cannot be definitively established, the results of this work support the application of a relative error range of -40% to +28% for 95% of the population, based on a statistical blood/breath ratio range of 1259:1 to 2679:1, and -46% to +42% for 99% of the population, based on a statistical range of 1128:1 to 2989:1.

Absorption↗
PubMed2005

The theory of transformations and autistic states. Autistic transformations: a proposal.

This work integrates two areas of thinking: one in which the author develops considerations regarding observation methods of mental phenomena in psychoanalysis according to Bion's theory of transformations; the other in which she is concerned with the investigation of primitive mental states--protomental states--more specifically, the autistic states of neurotic patients, described by Tustin. Some ideas on the 'philosophical' position underlying transformations theory are elaborated, particularly emphasizing the idea that the same phenomenon in psychoanalysis may be considered from different perspectives, as long as it is situated within the theoretical reference frame to which it belongs. The author considers the idea that this method of phenomenon observation is part of a wider context of general human knowledge, in which uncertainty and relativity of concepts are the main components. By adopting transformations theory as a perspective of phenomena observation that pervades the analytical meeting, the author questions whether it is possible to include other groups of transformation of emotional experiences in this theory, which shows particular phenomena with specific qualities, distinct from those emphasized by Bion. She hypothesizes that autistic phenomena present in neurotic patients, characterizing autistic states, may be considered and detached, making up a particular group of transformation of emotional experience, which analysts often face in their daily practice. She names this group 'autistic transformations'.

Autistic Disorder↗
PubMed1997

CD23 expression in transformed small lymphocytic lymphomas/chronic lymphocytic leukemias and blastic transformations of mantle cell lymphoma.

The immunophenotypic marker, CD23, has been shown to be a useful marker for the distinction of small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) from mantle cell lymphoma (MCL). The usefulness of this marker has not previously been analyzed in distinguishing various "large cell" transformations of SLL/CLL from blastic transformations of MCL (MCL-B). Thirteen cases of transformed SLL/CLL and six cases of MCL-B were analyzed for expression of CD23, either by flow cytometry of peripheral blood, bone marrow, or fresh tissue or by immunoperoxidase staining of paraffin-embedded archival tissue. All of the 13 cases of transformed SLL/ CLL expressed CD23 and all of the 6 cases of MCL-B were negative for CD23. Therefore, CD23 is retained in transformed SLL/CLL. It is a useful marker in distinguishing transformed SLL/CLL from MCL-B and thus might aid in distinguishing those cases that present de novo without a previous diagnosis of SLL/CLL or MCL.

Biomarkers, Tumor↗
PubMed1991

Viral and cellular oncogene expression during progressive malignant transformation of SV40 transformed human fibroblasts.

In vitro investigation of the multistep neoplastic progression which occurs during transformation of human cells has been hindered by resistance of human cells to both immortalization and tumorigenicity (Mut. Res. 199; 273, 1988). Previously our laboratory established a cell line, HSF4-T12, by transfection of normal human foreskin fibroblasts with the plasmid pSV3-neo which contains the early genes of simian virus 40 (SV40). A multistep progression in karyotypic alterations and transformed phenotype occurred resulting in a neoplastic cell line that was immortal, transformed, and tumorigenic. We have examined changes in the SV40 proteins, large T (T-antigen) and small t (t-antigen) antigens, and in the cellular protein, p53, during progressive transformation of these cells. Total viral protein expression relative to total cellular protein increased following immortalization of HSF4-T12 as did the ratio of T-antigen to t-antigen. Interestingly, no significant change in DNA content accompanied immortalization. However, during the progressive in vitro transformation of HSF4-T12 which occurred primarily post-immortalization, DNA index increased to 1.6 but only small additional increases in T-antigen expression were seen. No consistent or critical role for t-antigen in development of the tumorigenic phenotype was found in this system.

Antigens, Viral, Tumor↗
PubMed2006

Transforming growth factor-beta stimulates epithelial-mesenchymal transformation in the proepicardium.

The proepicardium (PE) migrates over the heart and forms the epicardium. A subset of these PE-derived cells undergoes epithelial-mesenchymal transformation (EMT) and gives rise to cardiac fibroblasts and components of the coronary vasculature. We report that transforming growth factor-beta (TGFbeta) 1 and TGFbeta2 increase EMT in PE explants as measured by invasion into a collagen gel, loss of cytokeratin expression, and redistribution of ZO1. The type I TGFbeta receptors ALK2 and ALK5 are both expressed in the PE. However, only constitutively active (ca) ALK2 stimulates PE-derived epithelial cell activation, the first step in transformation, whereas caALK5 stimulates neither activation nor transformation in PE explants. Overexpression of Smad6, an inhibitor of ALK2 signaling, inhibits epithelial cell activation, whereas BMP7, a known ligand for ALK2, has no effect. These data demonstrate that TGFbeta stimulates transformation in the PE and suggest that ALK2 partially mediates this effect.

Animals↗
PubMed1985

Further study of beta-TGFs released by virally transformed and non-transformed cells.

Chicken embryo fibroblasts sensitized by ts RSV respond to TGFs present in the media of non-transformed FR3T3 and NRK-4 rat cells and of the same cells transformed by KiMSV or RSV. They also respond to TGFs present in the media of BHK hamster cells transformed by MoMSV, PyV or RSV. Two other indicator rat cell lines, untransformed NRK-4 and FR3T3, sensitized by ts KiMSV, respond to the same TGF-containing media, and this response is increased by exogenous EGF. Normal FR3T3 cells failed to respond to any of the media. The most sensitive target cells were the ts KiMSV-FR3T3 cells at the restrictive temperature (39.5 degrees C). All the media tested on NRK-49F target cells required EGF for their TGF activity which was essentially dependent on prior activation by acidification. These data show that the above media from non-transformed or transformed cells contain beta-TGFs, with no detectable accompanying alpha-TGF activity. The release of and the response to these TGFs are not interdependent. A function of ts mutant src and k-ras viral oncogenes, still expressed at the restrictive temperature, can sensitize non-responsive cells, without there being any specificity towards the TGF producer cells.

Animals↗
PubMed1991

Tumor-promoting activity of Epstein-Barr-virus-inducing factor transforming growth factor type beta (EIF/TGF-beta) is due to the induction of irreversible transformation.

EBV-inducing factor/transforming growth factor type beta (EIF/TGF-beta) exhibits tumor-promoting activity for C3H-10T1/2 mouse fibroblasts in vitro. Treatment of C3H 10 T 1/2 fibroblasts seeded at low density with initiating doses of UV light, followed by culture in the presence of EIF/TGF-beta leads to the appearance of foci of stably transformed cells that have the potential to grow in soft agar. The promoting effect depends both on the dose of EIF/TGF-beta applied and its continuous presence for 2 to 3 weeks. In addition to its procarcinogenic effect in tumor promotion, EIF/TGF-beta exhibits a strong negative effect on transformed cells surrounded by normal cells, indicating a dual role of EIF/TGF-beta in carcinogenesis. The lack of completely transformed individual cells in the initiated cell population and the negative effect of EIF/TGF-beta on transformed cells in contact with normal cells exclude any possible explanation of the tumor-promoting effect of EIF/TGF-beta as being the result of a selection process due to the establishment of growth advantages for cells transformed by the initiator. The data, in fact, indicate that tumor promotion by EIF/TGF-beta implies the stable acquisition of distinct qualitative changes by the cells.

Animals↗
PubMed1994

Response of normal and oncogene-transformed human mammary epithelial cells to transforming growth factor beta 1 (TGF-beta 1): lack of growth-inhibitory effect on cells expressing the simian virus 40 large-T antigen.

The relationship between the expression of selected oncogenes having different modes of action and the loss of the capacity to respond in vitro to transforming growth factor-beta I (TGF-beta I) was analyzed in human mammary epithelial cells (MEC). Primary MEC cultures from healthy donors and the spontaneously immortalized MCF-10A cell line were used as normal controls. Various assays (employing both complete and chemically defined media) were used: short-term DNA synthesis, long-term cell proliferation under anchorage-dependent and -independent conditions, expression of surface-differentiation molecules. Whereas primary MEC and the MCF-10A cell line were fully responsive to the growth-inhibitory activity of TGF-beta I under different test conditions, MEC transformed by c-Ha-ras, c-erbB2, int-2, or SV40-large-T antigen were not inhibited by TGF-beta I in a short-term DNA-synthesis assay. However, in anchorage-dependent conditions TGF-beta I inhibited the proliferation of all lines investigated, with the exception of SV40-T-antigen-transformed MEC. The colony-formation assay in soft agar revealed that all lines, but not those expressing the int-2 or the SV40-T-antigen genes, were inhibited by TGF-beta I. Neutralizing antibody to TGF-beta had no significant effects on oncogene-transformed lines, suggesting that the endogenous production of an active form of this growth factor is not a major determinant in MEC transformation by the oncogenes investigated. The only observed effect of TGF-beta I on selected surface-differentiation molecules was that normal MEC produced increased levels of the human milk fat globule antigen-I. Thus it appears that the response of MEC to TGF-beta I is consistently attenuated by the insertion of a variety of oncogenes and that it is abolished only by the expression of the SV40-large-T antigen. Whereas no single in vitro assay was capable of accurately reflecting the actual responsiveness of different lines, the growth-curve assay in anchorage-dependent conditions was the best single predictive test.

Antigens, Surface↗
PubMed1993

Transforming growth factor beta 1 selectively regulates ornithine decarboxylase gene expression in malignant H-ras transformed fibrosarcoma cell lines.

Negative growth regulators such as the transforming growth factor beta (TGF-beta) family appear to be important inhibitors in most tissue types. However, inhibition of DNA synthesis and cell proliferation is frequently lost during malignant transformation, and in some cases, tumor cell proliferation is actually stimulated by TGF-beta. The present study demonstrates a novel link between alterations in TGF-beta regulation during malignant conversion, and the expression of ornithine decarboxylase, a key rate-limiting activity in the biosynthesis of polyamines, and an enzyme that plays an important role in cell growth and differentiation. A panel of radiation and H-ras transformed mouse 10T1/2 cell lines exhibiting increasing malignant potential was investigated for possible TGF-beta 1 mediated changes in ornithine decarboxylase gene expression. Selective induction of gene expression was observed since only H-ras transformed cell lines with malignant potential exhibited marked elevations in ornithine decarboxylase message levels. Ornithine decarboxylase gene expression in nontransformed 10T1/2 cells and cell lines capable of only benign tumor formation was unaffected by TGF-beta 1 treatment. H-ras transformed cells were transfected with a plasmid placing the TGF-beta 1 coding region under the control of a zinc sensitive metallothionein promoter. When these cells were cultured in the presence of zinc an elevation of TGF-beta 1 mRNA was observed within 30 min. This increase in TGF-beta 1 message closely coincided with an elevation in ornithine decarboxylase message, and preceded an induction of jun-B, an early response gene in cells sensitive to TGF-beta 1 stimulation. Evidence for regulation of ornithine decarboxylase gene expression by TGF-beta 1 at both transcription and posttranscription was found. Actinomycin D pretreatment of malignant cells prior to TGF-beta 1 exposure prevented the increase in ornithine decarboxylase message. Marked differences in the rates of ornithine decarboxylase message decay were observed when cells treated with TGF-beta 1 were compared to untreated controls, with the half-life of ornithine decarboxylase mRNA increasing from 2.5 h in untreated cells to 17.5 h in cells exposed to TGF-beta 1. In addition, evidence was obtained for a cycloheximide sensitive regulator of ornithine decarboxylase gene expression, since the presence of this protein synthesis inhibitor increased the levels of ornithine decarboxylase message, and this effect was synergistically augmented by exposure of cells to cycloheximide and induction of TGF-beta 1 gene expression together.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

Reversal of the transformed phenotype and inhibition of peptidylglycine alpha-monooxygenase in Ras-transformed cells by 4-phenyl-3-butenoic acid.

Recent studies have shown that the proliferation of some tumor cells is dependent on autocrine growth loops that require amidated autocrine growth factors. Peptidylglycine alpha-monooxygenase (PAM) is required for amidation of these growth factors and, therefore, this enzyme is an attractive target for anti-tumor compounds. 4-Phenyl-3-butenoic acid (PBA) is an irreversible turnover-dependent inhibitor of PAM in vitro and has been shown to decrease lung cancer cell proliferation by inhibiting the synthesis of amidated growth factors. We show here that PBA (0.1 mg/mL) inhibits the growth of Ras-transformed epithelial cells (WB-Ras) but has little effect on the proliferation of normal epithelial cells (WB-Neo). The methyl ester derivative of PBA (PBA-Me) at 10-fold lower concentration also exhibits a selective inhibition of Ras-transformed cell growth compared to normal epithelial cell growth. In addition, PBA produces a significant upregulation of gap junctional communication between WB-Ras cells following 2-5 day treatments, with a corresponding increase in the degree of connexin 43 phosphorylation and an increase in the number of connexin 43-containing plasma membrane gap junction plaques. Western blot analyses indicate no effect of PBA on the proportion of p21 Ras in the membrane versus cytosolic fractions or on p44/42 MAP kinase phosphorylation. Furthermore, the cell morphology of PBA-treated WB-Ras cells is altered, so as to more closely resemble that of non-transformed WB-Neo cells. PAM activity was assayed in both WB-Ras and WB-Neo cells, and we demonstrate that PBA at long treatment times (4 days) inhibits PAM activity in both cell types at concentrations that produce selective growth inhibition of WB-Ras cells. Shorter PBA treatment times (24 h), however, inhibit PAM activity in WB-Ras but not WB-Neo cells, an effect that was mimicked by PBA-Me. Taken together, these results clearly demonstrate that PBA returns Ras-transformed cells to a more normal phenotype, a finding consistent with the known increased dominance of the Ras signaling pathway in transformed epithelial cells.

Cell Line, Transformed↗
PubMed1986

SV40 large T-antigen and transformation related protein p53 are associated in situ with nuclear RNP structures containing hnRNA of transformed cells.

The localization of SV40 large T-antigen (T-Ag) and the cellular protein p53 in the nuclei of mouse and human SV40-transformed cells and of a methylcholanthrene-transformed mouse cell line, was studied. Their detection by ultrastructural immunocytochemistry with specific monoclonal antibodies employed two complementary methods used in parallel. These consisted of indirect immunoperoxidase labelling carried out before embedment on Triton-permeabilized cells, or indirect immunogold labelling applied to thin sections of cells embedded in Lowicryl K4M. The results indicate that in SV40-transformed cells both proteins are chiefly localized on peri- and interchromatin RNP fibrils. This shows that they occur in structures involved in the synthesis and processing of hnRNA. The nucleoli and chromatin did not appear to be labelled. In methylcholanthrene-transformed cells the protein p53 (in the absence of large T-Ag) was also detected on peri- and interchomatin fibrils. Taken together with recent results which demonstrated that, during lytic infection, T-Ag was associated chiefly with cellular chromatin (Harper, F, Florentin, Y & Puvion, E, Exp cell res 161 (1985) 434) [33], our experiments provide evidence that the transforming function of SV40 large T-Ag is dissociable from its function in SV40 lytic infection in terms of its subnuclear distribution.

Animals↗