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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammary tumor cell growth factor(s) has been identified in extracts of platelets from both male and female rats, as well as in extracts prepared from pooled outdated human platelets. When assayed by the growth promotion of MTW9/PL rat mammary tumor cells in culture, platelet extracts alone were able to support growth 50--75% as well as whole serum. The mitogenic activity from crude human platelet lysates was shown to be trypsin sensitive, relatively stable to extremes of pH, labile to heat treatment at 70 degrees, non-dialysable, ammonium sulfate precipitable, not removed by 56 degrees charcoal treatment, and of apparent molecular weight of 30,000 to 50,000 daltons as estimated by G-100 Sephadex chromatography. The platelet derived mammary growth factor activity was not replaced or potentiated by thrombin or known hormones and growth factors such as prolactin, insulin, 17-beta-estradiol, progesterone, hydrocortisone, L-thyroxine, and mouse epidermal growth factor. The experimental report demonstrates that platelets are a rich source growth factor activity for rat epithelial mammary tumor cells, and that the activity appears to be a polypeptide(s) different from other mitogenic activities known to influence growth of mammary tissue.
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PMID:Platelet derived growth factor(s) for a hormone-responsive rat mammary tumor cell line. 3 Jul 82

Hydrocortisone at physiological concentrations reversibly inhibits DNA synthesis in ST1 cells (a line of mouse fibroblasts possessing 40 chromosomes and derived from Swiss 3T3 cells). This inhibitory activity is a property of glucocorticoids, but the beta-OH of C-11 of glucocorticoids is not essential for the inhibition. The steroid hormone restores to ST1 cells dependency on serum, density, and anchorage for growth. When injected into nude mice, ST1 cells generated malignant invasive fibrosarcoma. Injections of dexamethasone into tumor-bearing animals blocked tumor growth. The steroid hormone seems to induce a reversible transition between a transformed and a "normal" phenotype. ST1 cells treated or untreated with hydrocotisone are not responsive to fibroblast growth factor, epidermal growth factor, or prostaglandin F2alpha whereas they are responsive to a factor that is a contaminant in bovine serum albumin.
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PMID:Steroid hormones mediate reversible phenotypic transition between transformed and untransformed states in mouse fibroblasts. 27 50

Tumor-promoting phorbol esters and related plant macrocyclic diterpenes inhibit the binding of epidermal growth factor to its receptors on HeLa cells. This effect shows marked structural specificity and correlates with other biological effects of these compounds on mouse skin and in cell culture systems. The active compounds inhibited binding of 125I-labeled epidermal growth factor with a 50 per-cent effective dose in the range of 10(-8) to 10(-9) M. Inhibition appears to be due to a decrease in the number of available epidermal growth factor receptors rather than a change in receptor affinity. These results suggest that certain biologic effects of tumor promoters may result from alterations in the function of cell surface receptors involved in growth regulation.
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PMID:Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors. 30 98

High affinity binding of epidermal growth factor (EGF) was detected with mouse epidermal cells in primary culture and with 2 epidermal cell lines maintained in permanent culture. EGF binding was inhibited by low concentrations of the tumor promoters 12-O-tetradecanoyl phorbol-13-acetate (TPA) and phorbol didecanoate (PDD), but not by the non-promoting phorbol esters 4-O-methyl TPA and 4 alpha-PDD.
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PMID:Binding of epidermal growth factor to primary and permanent cultures of mouse epidermal cells: inhibition by tumor-promoting phorbol esters. 31 29

In previous studies we demonstrated that the tumor-promoting agent 12-O-tetradecanoyl phorbol 13-acetate (TPA) and related macrocyclic diterpenes are potent inhibitors of the binding of epidermal growth factor (EGF) to its cell surface receptors in HeLa cells. The present study explores the specificity and mechanism of this effect. We have found that the same effect is observed in various cell types derived from mice, rats, or humans. In HeLa cells TPA inhibits the initial binding of EGF and also accelerates the loss of previously bound EGF from cells. The released EGF is recovered largely intact in the medium, indicating that TPA does not induce increased proteolysis or increased cellular internalization and degradation of EGF. The TPA effect on EGF receptors is mediated by a highly temperature-dependent process because TPA inhibition of EGF binding, and TPA-induced release of prebound EGF, are much greater at 37 degrees C or 22 degrees C than at 4 degrees C. A curious feature is that when cells are grown in TPA for one or more days they escape or become refractory to TPA inhibition of EGF binding. Taken together, these results suggest that TPA inhibits EGF binding not by binding directly to the "active site" of the EGF receptor but by indirectly altering the conformation or inducing the clustering of EGF receptors. These and other membrane effects of this tumor promoter suggest that it is a valuable probe for elucidating complex aspects of membrane structure and function.
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PMID:Mechanism of tumor promoter inhibition of cellular binding of epidermal growth factor. 31 58

Horseradish peroxidase (HRP) uptake was used to measure fluid-phase pinocytosis in monolayers of human epithelioid carcinoma cells (A-431). Histochemistry confirmed that cell-associated HRP was restricted to intracellular vesicles. Biochemical methods showed that HRP uptake in control cultures was directly proportional to the duration of exposure. The addition of low concentrations of epidermal growth factor (EGF) to the incubation media produced a 10-fold increase in the initial rate of pinocytosis. The EGF effect was rapid (within 30 s) but transient; the rate of pinocytosis returned to control levels within 15 min. Metabolic inhibitors reduced the EGF-stimulated rate of pinocytosis by greater than 90%. A conjugate of EGF and ferritin (F:EGF) was used to simultaneously compare the intracellular locations of EGF and HRP. Much of F:EGF was internalized in approximately 100-nm vesicles, while most of the HRP was located in much larger vesicles (range 0.1--1.2 micrometer) which also contained F:EGF. The tumor-promoter 12-0-tetradecanoyl-phorbol-13-acetate, which shares several biological activities with EGF, was also effective in stimulating an increase in the rate of pinocytosis.
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PMID:Rapid stimulation of pinocytosis in human carcinoma cells A-431 by epidermal growth factor. 31 44

Previous studies indicated that the potent tumor promoter 12--0--tetradecanoyl-phorbol-13-acetate (TPA) enhances transformation of rat embryo cells (2 degrees RE) by a mutant of human Ad5 (H5ts125). This study examines the effect of TPA, its structural analogs and epidermal growth factor (EGF) on anchorage-independent growth of a cloned population of H5ts125-transformed 2 degrees RE cells (clone E11). Both TPA and EGF (approximately 10(-8) M) induced a 3--5 fold increase in agar cloning efficiency of E11 cells. In addition, macroscopic colonies appeared earlier and were larger and more diffuse. The TPA analogs phorbol--12,13--didecanoate (PDD) and ingenol--3,20--dibenzoate also enhanced growth in agar of E11 cells, whereas phorbol, 4 alpha PDD and 4--0--meTPA, which are inactive as tumor promoters, failed to enhance agar growth. In contrast to the results obtained with E11 cells, TPA, PDD or ingenol--3,20--bidenzoate failed to induce growth in agar of normal 2 degrees RE cells. Dexamethasone (10(-5)--10(-6) M), trans retinoic acid (10(-5)--10(-6) M) and the protease inhibitors leupeptin, antipain and elastatinol did not inhibit the ability of TPA to enhance the growth of E11 cells in agar. The TPA-enhanced anchorage independence was a stable property, since subclones of E11 cells isolated from TPA-agar plates had a higher agar cloning efficiency than the parental E11 cells when retested in the absence of TPA. This effect of TPA does not appear to reflect simple selection of a subpopulation of cells. When the parental E11 cells were first cloned in monolayer culture in the absence of TPA, all ten randomly picked clones showed enhanced growth in agar in the presence of TPA. In addition, prior growth of E11 cells in monolayer culture in the presence of TPA did not enhance their subsequent growth in agar. This system therefore provides an example in which TPA appears to enhance the acquisition of a stable cell property, and thus may be a useful model for studying mechanisms of tumor promotion and progression.
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PMID:Tumor promoters and epidermal growth factor stimulate anchorage-independent growth of adenovirus-tranformed rat embryo cells. 31 62

The keratoacanthoma (KA) is a relatively common tumor which most often occurs on the sun-exposed areas of light skinned individuals of middle age and older. It may be viewed as an aborted squamous cell carcinoma that only in rare instances evolves into a progressively growing squamous cell carcinoma. As such, the recognition of the true nature and the proper management of this tumor is of considerable practical importance. The rapid evolution of a KA may be divided into a proliferative stage, a fully developed tumor, and an involuting stage. Within weeks it develops from a rapidly growing, firm, smooth nodule into a mature bud or dome-shaped tumor with a central keratotic core that finally degenerates into an involuting keratinous mass. Although the KA usually appears as a solitary lesion, multiple tumors may be found, as may a number of morphologic and syndromic variants, including the appearance of the KA in the Torre syndrome. The KA is likely to be derived from cells of the hair follicle. Its etiology is unclear, although ultraviolet light, viruses, oncogenic chemicals, and epidermal growth factor have been considered. The histologic features of the KA are often very similar to those of a cutaneous squamous cell carcinoma; however, the tumor architecture usually provides a basis for their distinction.
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PMID:The keratoacanthoma: a review. 39 96

The carcinogenic process is usually multifactor in its causation and multistep in its evolution. It is likely that entirely different molecular mechanisms underlie the many steps in this process. In contrast to initiating carcinogens, the action of the tumor-promoting phorbol esters does not appear to involve covalent binding to cellular DNA and they are not mutagenic. Recent studies in cell culture have revealed two interesting biologic effects of the phorbol esters and related macrocyclic plant diterpenes. The first is that at nanomolar concentrations they induce several changes that resemble those seen in cells transformed by chemical carcinogens or tumor viruses. These include altered morphology and increased saturation density, altered cell surface fucose-glycopeptides, decrease in the LETS protein, increased transport of deoxyglucose, and increased levels of plasminogen activator and ornithine decarboxylase. In transformed cells exposed to phorbol esters the expression of these features is further accentuated. Phorbol esters do not induce normal cells to grow in agar but they do enhance the growth in agar of certain transformed cells. The second effect of the phorbol esters is inhibition of terminal differentiation. This effect extends to a variety of programs of differentiation and is reversible when the agent is removed. With certain cell culture systems induction of differentiation, rather than inhibition, is observed. Both the transformation mimetic and the differentiation effects are exerted by plant diterpenes that have tumor-promoting activity but not by congeners that lack such activity. The primary target of phorbol esters appears to be the cell membrane. Early membrane-related effects include enhanced uptake of 2-deoxyglucose and other nutrients, altered cell adhesion, induction of arachidonic acid release and prostaglandin synthesis, inhibition of the binding of epidermal growth factor to cell surface receptors, altered lipid metabolism, and modifications in the activities of other cell surface receptors. A model of "two stage" carcinogenesis encompassing the known molecular and cellular effects of initiating carcinogens and tumor promoters is presented. According to this model, initiating carcinogens induce stable alterations in the cellular genome but these are not manifested until tumor promoters modulate programs of gene expression and induce the clonal outgrowth of the initiated cell.
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PMID:Action of phorbol esters in cell culture: mimicry of transformation, altered differentiation, and effects on cell membranes. 39 70

Phorbol esters stimulate 2-deoxy-D-glucose (DG) uptake in rodent and human cell cultures. The potent tumor promoting agent, 12-0-tetradecanoyl phorbol-13 acetate (TPA), induces a 12-fold stimulation in confluent 3T3 cells and 2.5-fold stimulation in HeLa cells. When a series of macrocyclic deterpenes are assayed, their relative potencies in stimulating DG uptake in 3T3 cells correlate with other known biologic effects of these compounds. On a molar basis, TPA is a much more potent stimulator of DG transport than insulin or epidermal growth factor. In HeLa cells, the ED50 value of the TPA effect is 0.2 nM. The increase in DG uptake occurs immediately after the addition of TPA, reaches a maximum at 90 minutes, persists for at least three hours after removal of TPA from the medium, and is temperature dependent. The stimulation is not inhibited by cycloheximide or actinomycin D. As in control cells, DG uptake in TPA treated cells is inhibited by p-hydroxymercuribenzoate, phyloridzin, cytochalasin B, and dexamethasone. Although the precise mechanism is not known, evidence is presented that the TPA stimulation of DG uptake is due to enhanced transport of the sugar rather than to effects on intracellular metabolism. The enhanced transport may be secondary to a more generalized change in membrane structure.
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PMID:Membrane effects of tumor promoters: stimulation of sugar uptake in mammalian cell cultures. 45 99


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