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Biomedical subjects

Y Kanno

Publications and source records attributed to Y Kanno.

At least 145 records · Page 8Linked to original sources
PubMed1985

Modulation of cell communication and carcinogenesis.

In this paper, recent studies on the role of cell communication in cancer induction, particularly in two-stage carcinogenesis, were reviewed. Cell communication has been proposed to play an important role in cell growth and differentiation since its discovery. The recent finding that tumor promoters inhibit cell communication supports this possibility. The inhibition of cell communication by phorbol ester tumor promoters was also shown to correlate with enhancement of in vitro carcinogenesis in Balb/c 3T3 cells. This strongly suggests that the blocked cell communication may play a crucial causative role in the process of carcinogenesis. Accumulated evidence indicates that phorbol ester may induce blockage of cell communication through binding to its membrane receptor which is presumably Ca2+/phospholipid-dependent kinase. cAMP enhances cell communication and protects its inhibition by phorbol ester, presumably through activating cAMP-dependent kinase. This indicates the possibility that the two kinases may be key elements for physiological regulation of cell communication. It is proposed that the disturbance of the kinase systems by endogenous and exogenous factors may be responsible for the promotion phase of cancer induction. However, the true physiological role of cell communication in carcinogenesis remains to be demonstrated more directly. Especially, what kinds of molecules can pass through the gap junction and regulate cell functions in a cell community must be challenged in future. Some such molecules were speculatively described in this review.

Animals↗
PubMed1985

Intercellular communication capacity as a possible determinant of transformation sensitivity of BALB/c 3T3 clonal cells.

While clonal cell variants of BALB/c 3T3 with high and low susceptibilities to ultraviolet radiation- and benzo(a)pyrene-induced transformation show similar intercellular communication capacities when they are in the growing phase, a significant loss in communication occurs at confluence only in transformation-sensitive clonal variant cells. A potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, which also enhances BALB/c 3T3 cell transformation induced by methylcholanthrene, inhibited intercellular communication of these variants to a similar extent. These results suggest that intrinsic differences in the control of intercellular communication may be a determinant of the susceptibility of these variants to the induction of transformation.

Animals↗
PubMed1984

Inhibition of cell communication between Balb/c 3T3 cells by tumor promoters and protection by cAMP.

The effect of phorbol ester tumor promoters on the communication between individual cells in confluent culture was studied using a fluorescent dye transfer method. Cell-cell communication between mouse Balb/c 3T3 cells and between Chinese hamster V79 cells was inhibited almost completely by tumor-promoting phorbol esters, but not by nonpromoting derivatives; the effect was reversed upon removal of the promoter. Intercellular communication between Balb/c 3T3 cells, but not Chinese hamster V79 cells, was increased significantly in the presence of dbcAMP and caffeine, and these compounds counteracted the effects of tumor promoters. Inhibition of cell communication by phorbol esters appears to be receptor-mediated, since specific binding of 3H-phorbol-12,13-dibutyrate to Balb/c 3T3 cells was inhibited only by compounds that also inhibit intercellular dye transfer. A study with cycloheximide suggests that the reversible inhibition of intercellular communication by phorbol esters may not need de novo protein synthesis, while upregulation of communication by cAMP requires protein synthesis.

Animals↗
PubMed1984

Protective effect of cAMP on tumor promoter-mediated inhibition of cell-cell communication.

The formation and maintenance of electrical cell coupling is inhibited by 100 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA). This inhibition could be prevented by db-cAMP and aminophylline when added together with TPA, though they did not restore the cell coupling once it had already been blocked by TPA. It is suggested that db-cAMP affects the early membrane effects of TPA in FL cells.

Aminophylline↗
PubMed1984

Monoclonal antibody ECCD-1 inhibits intercellular communication in teratocarcinoma PCC3 cells.

The monoclonal antibody ECCD-1 recognizing a certain class of cell surface proteins inhibits the Ca2+-dependent cell-to-cell adhesion in teratocarcinoma stem cells. In this paper, we studied the effect of ECCD-1 on cell-to-cell communication in PCC3 cells by measuring the transfer of lucifer yellow between cells. To this aim, PCC3 cells were cultured in the presence of ECCD-1 for various periods, and then the fluorescent dye was injected into a cell located in the center of cell colonies, followed by counting number of cells to which the dye was transferred. The results showed that ECCD-1 inhibits the dye transfer between cells, suggesting that the Ca2+-dependent cell-to-cell adhesion system (CDS) is essential for the functions of gap junction.

Animals↗
PubMed1984

Inhibitory action of thyrotropin-releasing hormone on serum amylase activity and its mechanism.

The effect of im administration of 500 micrograms TRH on serum amylase activity was studied in 34 normal women, 6 women with primary hypothyroidism, 1 woman with anorexia nervosa, 6 women with hyperthyroidism due to Graves' disease, and 5 women with renal failure on chronic hemodialysis. Serum amylase activity decreased significantly in 31 of 34 normal subjects 60 to 120 min after administration of TRH. However, amylase isoenzymes were not significantly affected after administration of TRH, suggesting that TRH equally affects pancreatic and salivary amylase activity. TRH was also effective in patients on chronic hemodialysis, indicating that TRH does not reduce serum amylase activity by increasing urinary excretion of amylase. Since TRH reduced serum amylase activity in hyperthyroid patients in whom TRH failed to stimulate TSH secretion, TRH does not reduce serum amylase activity through increased secretion of TSH. The action of TRH was not mediated by serum thyroid hormone levels since TRH was similarly effective in patients with hypothyroidism or hyperthyroidism. TRH did not inhibit or interfere with amylase determination when added in vitro to heparinized blood. Perfusion of the dog pancreas with TRH reduced amylase activity in pancreatic juice and pancreatic venous blood. The magnitude of the decrease was related to the dose of TRH used. Since decrease in amylase activity of the pancreatic juice preceded that in pancreatic venous blood, TRH probably directly acts on the pancreas to reduce amylase secretion. As a result, serum amylase activity decreased after administration of TRH.

Amylases↗
PubMed1983

Tumour promoter-mediated reversible inhibition of cell-cell communication (electrical coupling). Relationship with phorbol ester binding and de novo macromolecule synthesis.

A tumour promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), reversibly inhibits the onset and maintenance of cell-cell communication measured by electrophysiological method. We have now studied the mechanism by which TPA inhibits communication of human cells (FL) in culture. Using [3H]phorbol-12,13-dibutyrate [( 3H]PDBu), we found a class of specific, high-affinity, saturable binding sites in intact FL cells; they have a dissociation constant of 15.4 nM, and at saturation about 3 X 10(5) PDBu molecules were bound to each cell. The binding of [3H]PDBu to FL cells was inhibited by TPA, phorbol-12-13-didecanoate and mezerein, whereas phorbol and 4 alpha-phorbol-12-13-didecanoate had no effect. There is a close correlation between the ability of the former compounds to inhibit [3H]PDBu binding and their capacity to inhibit cell-cell communication. When FL cells are dispersed with EDTA and plated onto a culture dish, they start to couple electrically within 2 h; such cell coupling was not affected by the presence of cycloheximide or actinomycin D. TPA inhibits the formation of electrical cell coupling as well as its maintenance, even in the presence of cycloheximide; the recovery of cell-cell communication after the removal of TPA was not significantly affected by the addition of cycloheximide or actinomycin D. Taken together, these results suggest that TPA-mediated reversible inhibition of intercellular communication is mediated by specific binding of TPA to cellular receptors and that macromolecular synthesis is not necessary.

Binding Sites↗
PubMed1983

Membrane interaction and modulation of gene expression by tumor promoters.

Phorbol ester tumor promoters bind to specific cellular receptors (probably protein kinase C) and modulate membrane structure and function and gene expression of target cells. Using cell culture systems, we are studying the interaction of phorbol esters with the cellular membrane and subsequent modulation of gene expression. Our recent results can be summarized as follows: 1) specific binding of phorbol esters to mammalian cells can be inhibited by a human placental factor, which we have partially purified and characterized. 2) Phorbol ester tumor promoters reversibly inhibit intercellular communication, as measured by electrical coupling and dye transfer between cultured cells, suggesting that they inhibit both ionic and molecular transfer between cells. 3) In vitro transformation of Balb/c 3T3 cells results in blockage of intercellular communication between normal and transformed cells, indicating that blocked intercellular communication may play a role in cell transformation. 4) 12-O-Tetradecanoylphorbol-13-acetate (TPA) can continuously inhibit differentiation and globin gene expression in Friend erythroleukemia cells, without affecting their growth rate, for about 3 years. Both globin gene expression and terminal differentiation of Friend cells occur again upon removal of TPA from culture medium during such long-term culture.

Animals↗
PubMed1981

Tumor promoters cause a rapid and reversible inhibition of the formation and maintenance of electrical cell coupling in culture.

The effect of tumor promoters on electrical coupling between human FL cells was investigated with a microelectrode technique. When a low concentration (100 ng/ml) of 12-O-tetradecanoylphorbol 13-acetate (TPA) was added to culture medium, only 6% of the cells showed electrical coupling after 5 hr, whereas in control medium more than 90% of the cells were coupled. In the presence of TPA, cell coupling remained suppressed for at least another 19 hr. When TPA was washed out from the culture medium, the cells commenced electrical coupling: 90% of the cells were coupled within 4 hr of the removal of TPA, a rate very similar to that of nontreated control cells. Therefore, TPA-mediated inhibition of cell coupling is reversible. When TPA was added to a culture in which more than 90% of the cells had already established electrical coupling, the percentage of coupled cells decreased to 6% within 8 hr, indicating that TPA can also diminish already established cell coupling. Inhibition of cell coupling also was achieved with other mouse skin tumor promoters--phorbol 12,13-didecanoate, ingenol dibenzoate, and mezerein--whereas nonpromoting derivatives--phorbol and 4 alpha-phorbol 12,13-didecanoate-showed no effect. None of these compounds changed the membrane potential, membrane resistance, or growth rate of FL cells. Thus, it appears that TPA and structurally-related tumor promoters specifically disturb the formation or function, or both, of cell-cell junctions, without significantly affecting the general properties of the surface membrane or the growth of FL cells.

Cell Division↗