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Infection with a transforming growth factor alpha anti-sense retroviral expression vector reduces the in vitro growth and transformation of a human colon cancer cell line
No full textTransforming growth factor alpha (TGF alpha) is a growth factor produced by colon cancer cells which may function as an autocrine growth regulator. Therefore, the proliferation and transformation of colon cancer cells might be attenuated by blocking the production of endogenous TGF alpha. GEO cells, from a human colon carcinoma cell line that expresses TGF alpha and functional epidermal growth factor (EGF) receptors, were infected with a replication-defective, recombinant amphotropic retroviral expression vector containing the neomycin-resistance gene and a 435-bp ApaI-EcoRI coding fragment of the human TGF alpha cDNA oriented in the 3' to 5' direction under the transcriptional control of the heavy-metal-inducible mouse metallothionein I promoter. Following antibiotic selection, G418-resistant colonies were pooled and expanded into a cell line (GEO TGF alpha AS cells). A 50 to 70% inhibition in the production of secreted and cell-associated TGF alpha protein was observed in GEO TGF alpha AS cells that had been maintained in CdCl2-supplemented medium. Moreover, a growth inhibition of 70% and 50% was observed in CdCl2-treated GEO TGF alpha AS cells under anchorage-dependent and anchorage-independent culture conditions, respectively. In contrast, CdCl2 treatment of parental GEO cells had no significant effect upon these parameters. Our results suggest that TGF alpha may be involved in modulating the in vitro cell growth and transformation of human colon cancer cells that express both this growth factor and its cognate receptor
Differential growth sensitivity to 4-cis-hydroxy-L-proline of transformed rodent cell lines
Full text linkThe effect of 4-cis-hydroxy-L-proline (CHP), a proline analogue, on the anchorage-dependent and -independent growth of several transformed rodent cell lines was studied. Mouse NIH-3T3 fibroblasts transformed by a variety of different oncogenes (Ki-ras, mos, src, fms, fes, met, and trk) by a DNA tumor virus (SV40) or by a chemical carcinogen (N-methylnitrosourea) were all found to be more sensitive (50% inhibitory dose, 20 to 55 micrograms/ml) to the dose-dependent inhibitory effects of CHP on growth in monolayer culture than were NIH-3T3 cells (50% inhibitory dose, 120 micrograms/ml). CHP was generally found to be even more effective in inhibiting the growth of these transformed cells as colonies in soft agar than in monolayer cultures. In addition, rat embryo fibroblasts (CREF) and normal rat kidney fibroblasts (NRK) after transformation with a Ki-ras oncogene exhibit a similar increase in their sensitivity to CHP-induced growth inhibition. Treatment of NRK cells with transforming growth factor alpha (TGF-alpha) and beta (TGF-beta), which reversibly induces phenotypic transformation of these cells, increases their sensitivity to CHP to a level comparable with that observed in Ki-ras-transformed NRK cells (K-NRK). The growth inhibitory effects of CHP are reversible, since removal of CHP results in a normal resumption of cell growth. CHP uptake occurs primarily through the Na+- and energy-dependent neutral amino acid transport A system, which is 6- to 7-fold more elevated in K-NRK cells compared with NRK cells. Treatment of NRK cells with TGF-alpha and/or -beta increases the uptake of [3H]methylaminoisobutyric acid on the A system to a level that is similar to that found in K-NRK cells. The functions of the Na+/K+ and Na+/H+ exchange systems are apparently necessary for the enhanced A system activity, since ouabain and amiloride can inhibit the uptake of [3H]methylaminoisobutyric acid in K-NRK cells and in NRK cells treated with TGF-alpha and/or -beta. The activity of the A system is specifically increased in K-NRK and in TGF-alpha- and/or -beta-treated NRK cells, since the other two major neutral amino acid uptake systems, the ASC and the L systems, and the Ly+ system for basic amino acid uptake show no apparent changes in their activity in NRK cells after treatment with TGF-alpha and/or -beta or in these cells after transformation with the Ki-ras oncogene. These results suggest that the differential growth sensitivity to CHP of transformed rodent cells and of normal fibroblasts treated with TGF-alpha and/or -beta is due in part to an elevated uptake of this amino acid analogue on the neutral amino acid transport A system
Expression of cripto, a novel gene of the epidermal growth factor gene family, leads to in vitro transformation of a normal mouse mammary epithelial cell line
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Over-expression of the epidermal growth factor receptor in human breast cancer cells fails to induce an estrogen-independent phenotype
No full textTransforming growth factor-alpha messenger RNA localization in the developing adult rat and human mammary gland by in situ hybridization
No full textTransformation of mouse mammary epithelial cells with the Ha-ras but not with the neu oncogene results in a gene dosage-dependent increase in transforming growth factor-alpha production
No full textDifferential growth factor expression in transformed mouse NIH‐3T3 cells
No full textThe expression of growth factor‐specific mRNA transcripts and the presence of biologically active growth factors in the conditioned medium and in the cell extracts from mouse NIH‐3T3 cells transformed by different oncogences (Ki‐ras, mos, src, fms, fes, met, and trk), by DNA tumor virus (SV40), or by a chemical carcinogen (N‐nitrosomethylurea) were studied. In contrast to NIH‐3T3 cells or simain virus 40 (SV40)‐transformed 3T3 cells, all the other transformed NIH‐3T3 cell lines express a 4.5 kb transforming growth factor‐α (TGFα)‐specific mRNA transcript and secreted immunoreactive and biologically active TGFα ranging from 100 to 225 ng/108 cell/48 h. In addition, in the transformed cell lines that were secreting elevated levels of biologically active TGFα, there was a 75–95% reduction in the total number of epidermal growth factor receptors on these cells. A 2.6 kb TGFβ mRNA transcript and TGFβ protein in the conditioned medium (30–140ng/108 cells/48h) was also detected in those lines expressing TGFα. Basic fibroblast growth factor‐like activity (11–50 ng/108 cells) was detected in the cell lysates from NIH‐3T3 cells transformed with N‐nitrosomethylurea or with trk, where expression of specific 6.9 and 3.9 kb mRNA transcripts for basic fibroblast growth factor could also be found. B chain (c‐sis) expression of platelet‐derived growth factor was present only in trk‐transformed NIH‐3T3 cells in which specific c‐sis 6.5 and 4.6 kb transcripts were identified. In contrast, platelet‐derived growth factor A chain expression of 2.9 and 2.3 kb transcripts was found in ras‐, met‐, mos‐, and fms‐transformed NIH‐3T3 cells. These results suggest that the expression of different sets of growth factors is controlled in part by structurally distinct groups of transforming genes. Copyright © 1990 Wiley‐Liss, Inc
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