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R Dulbecco

Publications and source records attributed to R Dulbecco.

At least 55 records · Page 3Linked to original sources

Cell types and morphogenesis in the mammary gland.

Cell types present in the mammary gland and their evolution were studied by labeling female rats with radioactive thymidine at various phases of the estrus cycle. The results suggest that the stem cells for mammary development are present in the terminal end buds and that they generate a lineage for lumenal cells and possibly a distinct one for myoepithelial cells. Growth and differentiation are controlled by both hormones and local factors.

Animals↗

Generation of fibroblast-like cells from cloned epithelial mammary cells in vitro: a possible new cell type.

We have isolated clonal cell lines from a nitrosomethylurea-induced mammary tumor in Wistar--Furth rats. The epithelial-like cells of these lines give rise to fibroblast-like cells. A study of several markers showed that the epithelial-like cells are similar to epithelial mammary cells. The fibroblastic cells, however, were similar to stromal cells, except for the production of collagen IV. The events occurring in these cultures are identical to those observed in previously isolated mammary cultures [Bennett, D. C., Peachey, L. A., Durbin, H. & Rudland, P. S. (1976) Cell 15, 283--298], suggesting their generality. The fibroblast-like cells generated in culture may be a hitherto unrecognized type of mammary cell.

Animals↗

Differentiation and morphogenesis of mammary cells in vitro.

Cells of a mammary cell line isolated from a DMBA-induced rat mammary carcinoma undergo differentiation in vitro. A reversible differentiation leads to the formation of two types of microstructure (domes and ridges); this paper is concerned with the mechanism of dome formation. This differentiation is initiated by inducers, some of which are generated in the cultures and act locally; their effect is strongly dependent on cell concentration and requires hydrocortisone. There are, in addition, exogenous inducers as well as inhibitors. In the pathway to dome formation important roles are played by cAMP (probably both intracellular and extracellular), the organization of the cytoskeleton, and the Thy-1 antigen. The pathway and the significance of the phenomenon for mammary gland development are discussed.

Animals↗

Control of differentiation of a mammary cell line by lipids.

A rat mammary cell line (LA7) undergoes spontaneous differentiation into domes due to production of specific inducers by the cells. Some of these inducers may be lipids, and we show that lipids regulate this differentiation as both inducers and inhibitors. One inhibitor is the tumor promoter tetradecanoyl-13 phorbol 12-acetate. The inducers are saturated fatty acids of two groups: butyric acid and acids with chain lengths from C13 to C16, especially myristic acid (C14). Other inducers are myristoyl and palmitoyl lysolecithins, myristic acid methyl ester, and two cationic detergents with a tetradecenyl chain. We propose that the lipids with a C14-C16 alkyl chain affect differentiation by recognition specific receptors through their alkyl chains and that the effects obtained depend on the head groups. These lipids may be physiological regulators in the mammary gland.

Animals↗

Differentiation of a rat mammary cell line in vitro.

We have studied the development of fusiform (probably related to myoepithelial) cells in Rama 25 cultures [Bennett, D. C. Peachey, L. A., Durbin, H. & Rudland, P. S. (1978) Cell 15, 283--298]; we show that they are generated from special differentiated structures (projections) that contain a rapidly differentiating cell type (F-precursor cells). Clonal sublines isolated from projections develop in several directions under both environmental and genetic control. Some types of differentiation are reversible; others are irreversible. The various cell occurring in vitro may correspond to specific cell types in vivo.

Animals↗

Role of Thy-1 antigen in the in vitro differentiation of a rat mammary cell line.

A line of rat mammary cells, LA7, undergoes differentiation into domes or ridges or projections under partial medium control. Immunofluorescent studies show that at the time of dome formation the LA7 cultures express the Thy-1 antigen at the borders between cells. Exposure of the cultures to certain monoclonal anti-Thy-1.1 sera prevents formation of new domes and causes disappearance of preexisting ones; antisera to whole cells produce no visible effect. Cultures exposed to anti-Thy-1 sera at effective concentrations of antibody against domes show morphological changes and ridge formation. It seems that the specific interactions of these antisera with the Thy-1 antigen redirects the differentiation program of the cells.

Animals↗

State and organization of polyoma virus DNA sequences in transformed rat cell lines.

Polyoma virus-transformed rat cell lines were isolated as colonies growing in agar after infection of F2408 cells with low multiplicities of wild-type virus. Viral DNA present in the transformed cells was analyzed by fractionating the cellular DNA on agarose gels before and after digestion with various restriction endonucleases, followed by detection of the DNA fragments containing viral sequences using the procedure described by Southern (E. Southern, J. Mol. Biol., 98:503--515, 1975). Five lines, independently derived, were studied in detail. All five lines, when examined after a minimum number of passages in culture, contained both free and apparently integrated viral DNA. The free polyoma DNA in three of the lines was indistinguishable, by restriction enzyme analysis, from wild-type viral DNA, whereas the two other lines also contained smaller free DNA molecules which lacked parts of the wild-type genome. The integrated DNA in the five lines studies existed as head-to-tail tandem repeats of unit-length polyoma DNA covalently attached to nonviral DNA. The same five polyoma-transformed rat lines were examined after further passage in culture. Free viral DNA was then either undetectable or greatly reduced in amounts, whereas the high-molecular-weight, integrated units persisted after passage of the cells. The subclones, derived from one of the five lines selected for detailed analysis, showed some variations in the quantity and size of the free viral DNA as well as minor alterations in the pattern of the apparently integrated sequences.

Animals↗

Thy-1: a differentiation marker of potential mammary myoepithelial cells in vitro.

The rat mammary cell line Rama 25 [Bennett, D.C., Peachey, L.A., Durbin, H. & Rudland, P.S. (1978) Cell 15, 283--298] differentiates morphologically in vitro from a cuboidal form to a fusiform cell resembling myoepithelial cells. This differentiation occurs in all clonal isolates of the line. By using three different rabbit antisera specific for Thy-1, we have found that antigenic differentiation accompanies morphologic change to the fusiform state. Very few cuboidal cells had Thy-1 detectable on their surfaces in the living state; but after acetone fixation cytoplasmic Thy-1 was detected by immunofluorescence in all cells of the cuboidal type. Thy-1 specificity was established by the fact that immunofluorescence induced by rabbit anti-rat thymocyte serum was abolished by absorption with rat brain but not with erythrocytes, kidney, or liver; immunofluorescence induced by rabbit antiserum to purified Thy-1 glycoproteins from mouse lymphomas was absorbed by Thy-1 positive mouse and rat lymphomas. Surface Thy-1 provides a potentially valuable antigenic marker in the Rama 25 line for studying the differentiation of mammary myoepithelial cells.

Animals↗

Virus-specific proteins in the plasma membrane of cells lytically infected or transformed by pol-oma virus.

Antisera, raised in rats, containing specificities directed against tumor antigen of polyoma virus also react with several proteins present in the plasma membrane of mouse cells infected with the virus. The main component has an apparent molecular weight of 55,000. The appearance of this protein after infection with early temperature-sensitive A mutants was temperature-dependent like tumor antigen itself. Pulse and chase isotope experiments suggest that this protein originates from a precursor, perhaps by cleavage; its production appears to be facilitated by the A mutation. Two other components with apparent molecular weights of 61,000 and 28,000 were also present but were more variable from experiment to experiment. All proteins were absent from the plasma membranes of cells infected with a transformation-defective mutant, NG-18. Up to four virus-specific proteins could be isolated from the plasma membranes of rat, hamster, and mouse cells transformed by the virus. The possible role of the plasma membrane proteins in cell transformation is discussed.

Animals↗

Characterization of polyoma virus T antigen.

High-titer antiserum raised in rats against the tumor (T) antigen of polyoma virus was used to purify the T antigen by the Staphylococcus protein A antibody adsorbent technique. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis allowed the identification of a protein with an apparent molecular weight of 100,000-108,000 as a major component induced in lytically infected mouse cells. In cells infected by ts A mutants this component was temperature sensitive. Several minor components were also observed. In pulse and chase experiments there was a slight decrease in electrophoretic mobility of T antigen during the chase period at the permissive temperature, suggesting that the T antigen is a modified protein. In two lines of transformed cells, the amount of T antigen seemed to be considerably less than in lytically infected cells, but the size of the antigen appeared to be equal.

Antibody Specificity↗

Francis Peyton Rous.

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History, Modern 1601-↗

Augmentation of cytotoxic drug action and X-irradiation by antibodies.

The effect of an antiserum containing antibodies against cell surface components of PyBHK cells on the action of certain anticancer agents has been studied using a colony formation inhibition assay. The effects of x-rays, chlorambucil, CCNU and possibly ICRF 159 are augmented by the antiserum whereas methotrexate and vinblastine are not.

Antibodies, Neoplasm↗

Induction of growth in resting fibroblastic cell cultures by Ca++.

Of all the components of the culture medium, only CaCl2 induces DNA replication when added to resting cultures of Balb/c 3T3 cells. The effect is present even in a serum-free medium. Increasing the Ca++ concentration above the standard 1.8 mM in the medium of a new culture increases the total number of cells ultimately produced, without affecting the initial cell growth rate. This effect is synergistic with that of serum. The elevated Ca++ concentration also induces striking morphological changes. The Ca++ effect could not be reproduced by a Ca++ ionophore. These observations afford a new tool for studying how the various intracellular events following the addition of growth factors to resting cultures are involved in the control of cellular growth.

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