Transcriptional modulation of transin gene expression by epidermal growth factor and transforming growth factor beta

1988 ◽  
Vol 8 (6) ◽  
pp. 2479-2483
Author(s):  
C M Machida ◽  
L L Muldoon ◽  
K D Rodland ◽  
B E Magun

Transin is a transformation-associated gene which is expressed constitutively in rat fibroblasts transformed by a variety of oncogenes and in malignant mouse skin carcinomas but not benign papillomas or normal skin. It has been demonstrated that, in nontransformed Rat-1 cells, transin RNA expression is modulated positively by epidermal growth factor (EGF) and negatively by transforming growth factor beta (TGF-beta); other peptide growth factors were found to have no effect on transin expression. Results presented here indicate that both protein synthesis and continuous occupancy of the EGF receptor by EGF were required for sustained induction of transin RNA. Treatment with TGF-beta inhibited the ability of EGF to induce transin, whether assayed at the transcriptional level by nuclear run-on analysis or at the level of transin RNA accumulation by Northern (RNA) blot analysis of cellular RNA. TGF-beta both blocked initial induction of transin transcription by EGF and halted established production of transin transcripts during prolonged treatment. These results suggest that TGF-beta acts at the transcriptional level to antagonize EGF-mediated induction of transin gene expression.

1988 ◽  
Vol 8 (6) ◽  
pp. 2479-2483 ◽  
Author(s):  
C M Machida ◽  
L L Muldoon ◽  
K D Rodland ◽  
B E Magun

Transin is a transformation-associated gene which is expressed constitutively in rat fibroblasts transformed by a variety of oncogenes and in malignant mouse skin carcinomas but not benign papillomas or normal skin. It has been demonstrated that, in nontransformed Rat-1 cells, transin RNA expression is modulated positively by epidermal growth factor (EGF) and negatively by transforming growth factor beta (TGF-beta); other peptide growth factors were found to have no effect on transin expression. Results presented here indicate that both protein synthesis and continuous occupancy of the EGF receptor by EGF were required for sustained induction of transin RNA. Treatment with TGF-beta inhibited the ability of EGF to induce transin, whether assayed at the transcriptional level by nuclear run-on analysis or at the level of transin RNA accumulation by Northern (RNA) blot analysis of cellular RNA. TGF-beta both blocked initial induction of transin transcription by EGF and halted established production of transin transcripts during prolonged treatment. These results suggest that TGF-beta acts at the transcriptional level to antagonize EGF-mediated induction of transin gene expression.


Author(s):  
Seyyed Jafar NOSRATABADI ◽  
Nasim HAYATI ROODBARI ◽  
Mohammad Hossein MODARRESI ◽  
Alireza FARSINEJAD ◽  
Majid FASIHI HARANDI

Background: In recent decades platyhelminths have been used as model organisms to address some of the fundamental questions related to the growth and development of animal organisms. Epidermal Growth Factor Receptors (EGFR) and Transforming Growth Factor beta (TGF-beta) have a regulatory role in the growth and development of Echinococcus species. This study determined the effect of alpha-tocopherol on the expression of EGFR and TGF-beta genes in three in vitro developmental stages of E. granulosus. Methods: E. granulosus protoscoleces were cultured in diphasic medium containing bovine serum and CMRL 1066. Three developmental stages of E. granulosus, i.e. invaginated protoscoleces, evaginated protoscoleces and three-proglottid worms, were treated by alphatocopherol (250 μg/ml for 36 h) and the expression of EGFR and TGF-beta genes were evaluated by using qPCR analysis. Results: Intact protoscoleces were successfully developed to the segmented worms in diphasic culture media. Higher levels of both EGFR and TGF-beta gene expression were observed in the invaginated protoscoleces as well as the segmented worms in comparison to the non-treated controls. Conclusion: Administration of alpha-tocopherol to different developmental stages of E. granulosus significantly enhanced EGFR and TGF-beta expression in the parasite. Both oxidant and non-oxidant activities of alpha-tocopherol could explain the study findings. Overexpression of the genes could in turn enhance growth factor effects and facilitates the viability of the parasite.


1985 ◽  
Vol 100 (5) ◽  
pp. 1508-1514 ◽  
Author(s):  
J Massagué

The epidermal growth factor (EGF) receptor mediates the induction of a transformed phenotype in normal rat kidney (NRK) cells by transforming growth factors (TGFs). The ability of EGF and its analogue TGF-alpha to induce the transformed phenotype in NRK cells is greatly potentiated by TGF-beta, a polypeptide that does not interact directly with binding sites for EGF or TGF-alpha. Our evidence indicates that TGF-beta purified from retrovirally transformed rat embryo cells and human platelets induces a rapid (t 1/2 = 0.3 h) decrease in the binding of EGF and TGF-alpha to high-affinity cell surface receptors in NRK cells. No change due to TGF-beta was observed in the binding of EGF or TGF-alpha to lower affinity sites also present in NRK cells. The effect of TGF-beta on EGF/TGF-alpha receptors was observed at concentrations (0.5-20 pM) similar to those at which TGF-beta is active in promoting proliferation of NRK cells in monolayer culture and semisolid medium. Affinity labeling of NRK cells and membranes by cross-linking with receptor-bound 125I-TGF-alpha and 125I-EGF indicated that both factors interact with a common 170-kD receptor structure. Treatment of cells with TGF-beta decreased the intensity of affinity-labeling of this receptor structure. These data suggest that the 170 kD high-affinity receptors for EGF and TGF-alpha in NRK cells are a target for rapid modulation by TGF-beta.


The Prostate ◽  
1992 ◽  
Vol 21 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Debra M. Sutkowski ◽  
Chau-Jye Fong ◽  
Julia A. Sensibar ◽  
Alfred W. Rademaker ◽  
Edward R. Sherwood ◽  
...  

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 118-124 ◽  
Author(s):  
M Chang ◽  
Y Suen ◽  
SM Lee ◽  
D Baly ◽  
JS Buzby ◽  
...  

Hematopoiesis is developmentally immature in the newborn compared with the adult. Diminished gene expression of several positive hematopoietic regulators has been observed in activated cord compared with adult peripheral blood mononuclear cells (MNC; Cairo et al. Pediatr Res, 30:362, 1991 and Cairo et al, Pediatr Res, 31:574, 1992). However, altered expression of negative hematopoietic regulators during states of increased demand may also contribute to the pathogenesis of newborn dyshematopoiesis. To test this hypothesis, we measured protein levels of transforming growth factor-beta 1 (TGF-beta 1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the conditioned media of human umbilical cord and adult MNC using specific enzyme-linked immunosorbent assays. There was significantly less TGF-beta 1 in culture supernatants of cord versus adult MNC after 24, 72, and 120 hours of stimulation (P < .05), and significantly less MIP-1 alpha in cord versus adult supernatants after 72 hours and 120 hours of stimulation (P < .01). We then examined the mRNA expression of the negative regulators TGF-beta 1, MIP-1 alpha, and interleukin-8 (IL-8) in cord and adult MNC using Northern blot hybridization followed by quantitative densitometry. Cord MNC expressed significantly less TGF- beta 1 mRNA than adult MNC 6 hours and 72 hours after stimulation (P < .001). Cord MNC expressed significantly less MIP-1 alpha mRNA than adult MNC 6 hours (P < .01), 24 hours (P < .001), and 72 hours after stimulation (P < .001). Cord MNC also expressed significantly less IL-8 mRNA than adult MNC 6 hours after stimulation (P < .001). Therefore, decreased mRNA accumulation appears to coincide with reduced cytokine expression in the activated cord MNC. There were no significant differences in the transcription rates determined by nuclear run-on assay of either the TGF-beta 1 or MIP-1 alpha gene in cord versus adult MNC after 6 hours of stimulation, suggesting that the reduced TGF-beta 1 and MIP-1 alpha mRNA in activated cord MNC may be secondary to alteration in posttranscriptional regulation. The present results, together with those of our previous studies, suggest that the altered expression of both positive and negative hematopoietic regulators may be involved in the immaturity of host defense in human neonates.


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