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Biomedical subjects

A E Berman

Publications and source records attributed to A E Berman.

At least 19 recordsLinked to original sources
PubMed2006

The role of beta1 integrin subfamily in anchorage-dependent apoptosis of breast carcinoma cells differing in multidrug resistance.

Integrin expression was investigated in MCF-7 human breast adenocarcinoma line and in the MCF-7Dox line, which was selected from MCF-7 by a resistance to multiple antitumor drugs (MDR). We have shown that acquisition of MDR was accompanied by a drastically reduced expression of some integrins of the beta1-subfamily (alpha2beta1, alpha3beta1, alpha6beta1) and of alpha vbeta5 intergin in the adenocarcinoma cells. In contrast, expression of alpha5beta1 integrin was markedly increased in the MDR cells. Along with multiple antitumor drug resistance, MCF-7Dox cells demonstrate elevated resistance to anchorage-dependent apoptosis (anoikis) and enhanced in vitro invasive activity. To elucidate the implication of beta1-integrins in the above phenotypic modifications, the effect of beta1-integrin signaling was assayed. Stimulation of beta1-mediated signaling was accomplished by treating of the cells with antibodies to the beta1-subunit common for members of the beta1-subfamily. These data show that activation of beta1-integrin signaling markedly upregulated anoikis of the adenocarcinoma cells.

Anoikis↗
PubMed2004

Expression and role of integrins in invasive activity of oncotransformed fibroblasts differing in spontaneous metastasizing.

Four closely related lines of RSV-transformed Syrian hamster fibroblasts differing drastically in their spontaneous metastatic capacity were investigated for the surface expression of integrins, in vitro invasion, and production of MMP-2 collagenase. The highly metastasizing HET-SR-2SC-LNM cells differ from the lowly metastasizing parental HET-SR cells in a high level of the surface expression of the collagen-specific alpha1beta1, alpha2beta1, and alphavbeta3 integrins, a high invasive activity, and an increased production of MMP-2. The same properties are characteristic for the actively metastasizing cells of the independent HET-SR-1 line. The lowly metastasizing fibroblasts that are derived from HET-SR-2SC-LNM retain a high level of the expression of the alpha1beta1 and alpha2beta1 integrins, but, unlike the parental line, they exhibit a decreased expression of the alphavbeta3 integrin, invasion in Matrigel, and MMP-2 production. Substrate stimulation of the signal function of the collagen-specific integrins increases the production of MMP-2 by the metastatically active fibroblasts. Inhibition of the signal activity of the integrins by RGD-containing pentapeptide or by genistein reduces markedly in vitro invasion in Matrigel and MMP-2 production. The role of specific properties of the extracellular matrix surrounding tumor cells and of specific surface integrins expressed in these cells in developing of the malignant phenotype is discussed.

Animals↗
PubMed2003

Role of integrin alphavbeta3 in substrate-dependent apoptosis of human intestinal carcinoma cells.

Incubation of human intestinal carcinoma Caco-2 cells in suspension (i.e., in the absence of substrate contacts) leads to massive cell death by apoptosis. Since this type of apoptosis has been referred to as anoikis, we designated these cells as anoikis-positive. However, a minor proportion of Caco-2 cells, designated as anoikis-negative, survived in suspension. Extended incubation of the cells in suspension resulted in the reduction of the number of viable cells. In comparison to the original Caco-2 cell population, the anoikis-negative cells demonstrated markedly decreased levels of expression of integrin alphavbeta3 on the cell surface and of transcription of the alphav subunit gene. Activation of the signaling function of alphavbeta3 in the original Caco-2 cells led to substantial stimulation of anoikis, while the inhibition of expression of this receptor resulted in better resistance of the cells to anoikis. The data provide the first evidence that alphavbeta3 integrin can generate apoptosis-stimulating signals.

Anoikis↗
PubMed2003

Integrins: structure and signaling.

Integrins are cell surface transmembrane glycoproteins that function as adhesion receptors in cell-extracellular matrix interactions and link the matrix proteins to the cytoskeleton. The family of human integrins comprises 24 members, each of which is a heterodimer consisting of 1 of 18 alpha- and 1 of 8 beta-subunits. Integrins play an important role in the cytoskeleton organization and in transduction of intracellular signals, regulating various processes such as proliferation, differentiation, apoptosis, and cell migration. This review summarizes current views on the structure of integrins, integrin associated proteins, and biochemical mechanisms underlying their signaling functions.

Animals↗
PubMed2001

Integrin alphavbeta3 promotes anchorage-dependent apoptosis in human intestinal carcinoma cells.

A population of cells surviving during prolonged incubation in suspension (anoikis-negative cells) were selected from the original anoikis-positive human intestinal carcinoma cell line Caco-2. Anoikis-negative cells are characterized by a strong transcriptional downregulation of the alphav-integrin chain as detected by FACS analysis, RT-PCR and Northern blotting. This finding suggested that alphav-integrin generates a signal stimulating apoptosis of Caco-2 cells upon their detachment from the extracellular matrix. Two lines of evidence supporting this suggestion were provided. First, activation of the alphavbeta3 integrin on Caco-2 cells by their treatment with an alphavbeta3-specific monoclonal antibody resulted in marked stimulation of anoikis. Second, treatment of Caco-2 cells with alphav-specific antisense oligonucleotide resulted in downregulation of the expression of alphav chain and in elevated resistance of these cells to anoikis. Thus, for the first time, our data prove that alphavbeta3 integrin can be an active transducer of apoptosis-stimulating signals generated in response to disruption of the cell-matrix contacts.

Anoikis↗
PubMed2000

Integrins: structure and functions.

Integrins are cell surface transmembrane glycoproteins which perform receptor functions in cell interactions with the extracellular matrix and cell-cell contacts. Another function of integrins is transduction of signals which mediate the effects of the matrix on the physiological activity of cells (motility, proliferation, differentiation, etc.). Contemporary views on the molecular structure of integrins and their involvement in the organization of the cytoskeleton and control of gene activity are presented. Biochemical mechanisms, by which the signal functions of integrins are realized, are discussed. The data on the participation of integrins in oncogenic cell transformation, metastasis, and apoptosis are analyzed.

Animals↗
PubMed1997

Fucoidan inhibits leukocyte recruitment in a model peritoneal inflammation in rat and blocks interaction of P-selectin with its carbohydrate ligand.

Neutrophil recruitment into systemic inflammatory sites in vivo is thought to be initiated by selectin-mediated endothelial adherence. The effect of fucoidan (natural sulfated polymer of L-fucose) on the selectin dependent PMN migration into rat peritoneum following the induction of inflammation by peptone injection was studied. Peritonitis was characterized by an increase in the total cell number (from 45.3 x 10(6) to 91.6 x 10(6)/rat), and by highly elevated PMN content (from 0.2% to 58%) in the rat peritoneal cavity 3 h after peptone injection. Intravenous administration of fucoidan was found to reduce, in a dose-dependent manner, neutrophil migration into peritoneum. Fucoidan in a dose as low as 0.8 mg per rat caused 96.8% reduction of neutrophil extravasation. The inhibitory effect of fucoidan was also dependent on the time intervals between the peptone and fucoidan injections. The maximal inhibitory effect of fucoidan was observed within the first 15 min after the induction of peritonitis and it was maintained at a level of 80% during 1.5 h. Administration of fucoidan 2.5 h after peptone injection had practically no effect on PMN extravasation. Since P-selectin is known to play a key role at the earlier stages of PMN extravasation, it was suggested that the inhibitory effect of fucoidan was mostly due to its interaction with P-selectin. The in vitro experiments demonstrated the high affinity of fucoidan for both isolated P-selectin and P-selectin in plasma membranes of activated platelets.

Animals↗
PubMed1997

Integrin expression and collagenase activity of RSV-transformed Syrian hamster fibroblasts, differing in spontaneous metastasizing.

The expression of extracellular matrix (ECM) specific receptors, integrins, and the activities of type IV collagenase and interstitial collagenase were investigated in two strains of oncogenically transformed fibroblasts, drastically differing in spontaneous metastasizing. Both strains were shown to express quite limited patterns of integrins. Of those, alpha 5 beta 1 integrin is greatly reduced on highly metastatic (HM) cells, while the expression of alpha v beta 3 is strongly suppressed on lowly metastatic (LM) fibroblasts. No differences between the strains were found in either intracellular or secreted activities of type IV collagenase, while the activity of interstittial collagenase, secreted by HM cells, was twice as much as secreted by LM cells. The results imply the role of cooperated modifications of integrin-directed cell-ECM interaction and collagenase activity in establishing a metastatic phenotype.

Animals↗
PubMed1992

Heparin-binding fibronectin fragments containing cell-binding domains and devoid of hep2 and gelatin-binding domains promote human embryo fibroblast proliferation.

The proliferation promoting activity of various proteolytic fragments of human plasma fibronectin was assayed. Study of this activity in fragments, purified by affinity chromatography, has shown that only heparin-binding fragments were capable of promoting fibroblast proliferation while gelatin- and fibrin-binding fragments were not. Heparin-binding fragments with high affinity for heparin were characterized by high activity levels while those with low heparin affinity were inactive. Heparin-binding fragments with the highest proliferation promoting activity contained the cell-binding domain and were virtually devoid of the hep2, hep1 and gelatin-binding domains.

Cell Division↗
PubMed1990

Secretion and intracellular degradation of collagen in cultures of normal and SV-40-transformed human fibroblasts.

With a pulse-chase technique, secretion and intracellular degradation of collagen were investigated in human cultured normal and SV-40-transformed fibroblasts. Normal cells at a proliferative phase of growth secreted collagen more actively than the stationary phase (resting) cells. Transformed fibroblasts secreted protein at a lower rate than both normal cell types. Resting and dividing normal cells displayed no differences in the rates of intracellular collagen degradation at the various stages of the chase period. Transformed cells did not differ from the normal ones in collagen degradation rates at the first hour of the chase period while at later times in the chase period, the total amount of degraded collagen was reduced by 20-30% in the transformed vs normal cultures. The data are discussed in the view of possible relations between the various mechanisms of intracellular transport and degradation of collagen.

Cell Division↗
PubMed1988

[Functional and structural characteristics of polyribosomes associated with chick embryo cell nuclei].

Polyribosomes bound to the outer nuclear membrane was isolated from purified preparations of chicken embryo cell nuclei. These polyribosomes were shown to consist fractions forming unstable complexes with the nuclear membrane which can be separated from the latter by treatment with high ionic strength buffer solutions. Using sedimentation and gradient density analyses, the nuclei-bound RNP complexes were shown to be predominantly composed of 80S monosomes which take an active part in collagen polypeptide synthesis in cell-free protein-synthesizing systems. A comparison of sedimentation properties and collagen-synthesizing activity of nuclei-bound polyribosomes and cytoplasmic polyribosomes forming unstable complexes with endoplasmic membranes, it was concluded that the nuclei-bound 80S monosomes are an early step in the formation of cytoplasmic polyribosomes.

Animals↗
PubMed1987

[Biosynthesis and secretion of collagen in normal and SV-40 virus-transformed human embryonal fibroblasts].

The biosynthesis and secretion of collagen proteins was studied in cultures of normal human embryo fibroblasts at different passages and growth stages as well as in cultures of human embryo fibroblasts transformed by oncogenic virus SV-40. It was found that normal fibroblasts maintain at a constant level the collagen synthesis throughout 20 passages, which is typical of proliferating and resting cells. Virus-transformed cells produce 3-4 times less collagen proteins on a per cell count. Normal and transformed fibroblasts do not differ in terms of total protein synthesis. Secretion of collagen and non-collagen proteins in transformed cell cultures appeared to be much lower than in normal cell cultures. Study of synthesized proteins by polyacrylamide gel electrophoresis showed that both types of cells secrete collagen proteins predominantly as polymers containing interchain S-S bonds of 3-helix molecules. Study of the protein-synthesizing activity of two polysomal fractions, i.e. membrane bound and free polysomes, isolated from the cells of both types in a cell-free system showed that membrane-bound polysomes from transformed fibroblasts synthesize collagen much less actively in comparison with normal cells. However, in transformed cells free polysomes, in contrast with normal cells, are active participants of a cell-free collagen protein synthesis.

Cell Line↗
PubMed1985

[Characteristic features of protein synthesis in the extracellular matrix during tumor growth].

Changes in the biosynthesis of basic extracellular proteins (e.g., collagen proteins, fibronectins, proteoglycans) in the course of neoplastic growth are reviewed. Some peculiarities of quantitative changes in the biosynthesis and modifications of the primary structure of the above macromolecules are discussed in terms of neoplastic cell differentiation. The main emphasis is laid on the mechanisms underlying the disturbances in the biosynthetic activity of extracellular matrix proteins in neoplastic cells at different steps of protein synthesis and extracellular degradation of protein molecules.

Animals↗
PubMed1981

[Polyribosomes loosely bound to endoplasmic reticulum membranes as an early step in the formation of a membrane-polyribosome complex].

Fractionation of polyribosomes tightly and loosely bound to the endoplasmic reticulum membranes in a sucrose density gradient was carried out. The obtained fractions (mono- and disomes, light and heavy polyribosomes) were analyzed in a homologous cell-free protein-synthesizing system in order to determine their total protein- and collagen-synthesizing activities. All the three fractions prepared by fractionation of the loosely bound polyribosomes were found to be actively involved in protein synthesis translation. In case of tightly bound polyribosomes only the fractions of light and heavy polyribosomes could actively synthesize the protein. Study of collagen synthesis in the given fractions revealed that in tightly bound polyribosomes this synthesis is localized in the light and have polyribosomal fractions, while in loosely bound ones only the fractions of mono- and disomes are responsible for active collagen synthesis. Based on the present-day concepts on the nature of bonds formed by interaction between the endoplasmic reticulum membranes and polyribosomes the polyribosomes loosely bound to the membranes cna be considered as an early step in the formation of a membrane-polyribosome complex.

Animals↗
PubMed1980

[Biosynthesis of collagen in a cell-free system from wheat germ on poly(A)-RNA isolated from membrane-bound polyribosomes of chicken embryos].

The total protein-synthesizing and collagen-synthesizing activities of poly(A)-containing RNA from the membrane-bound polyribosomes of chicken embryos were studied under various conditions in a cell-free wheat germ system. The optimal concentrations of poly(A)-RNA, mono- and bivalent cations and spermine necessary for the translation of collagen and non-collagen proteins were determined. It was shown that within a wide range of K+ and Mg2+ concentrations in a cell-free system the poly(A)-RNAs studied are very actively involved in the translation of non-collagen proteins. At the same time the bacterial collagenase-cleavable polypeptides synthesized on poly(A)-RNA from the membrane-bound polyribosomes were identified only after addition of polyamine -- spermine (40 mk/M) to the system. In this case the relative level of collagen polypeptide synthesis remains constant within a wide range of concentrations of mRNA, K+ and Mg2+ in the system. Collagen-synthesizing activity of poly(A)-RNA from membrane-bound polyribosomes in a heterologous cell-free system as compared to that of membrane-bound polyribosomes in a homologous system showed that these polyribosomes can be effectively used for isolation of collagen mRNA.

Animals↗