In vivo evaluation of epidermal growth factor and transforming growth factor β1 in mouse tumor models

1990 ◽  
Vol 37 (6) ◽  
pp. 883-887 ◽  
Author(s):  
Simon P. Robinson ◽  
William C. Rose ◽  
AnnaMaria Casazza
1996 ◽  
Vol 148 (1) ◽  
pp. 87-94 ◽  
Author(s):  
A J Cowin ◽  
E L Heaton ◽  
S H Cheshire ◽  
S P Bidey

Abstract The present study has investigated an involvement of autocrine transforming growth factor-β1 (TGF-β1) in regulating the proliferative response of porcine thyroid follicular cells (TFCs) to epidermal growth factor (EGF) and TSH. Primary monolayer TFC cultures exposed to EGF over the range 0–0·4 nmol/l showed a dose-dependent increase in [methyl-3H]thymidine incorporation, whereas higher EGF doses were associated with a reduction in the level of [methyl-3 H]thymidine incorporation. TGF-β immunoneutralisation had little effect on the stimulatory action of low EGF doses, but led to an increase in [methyl-3H]thymidine incorporation at higher EGF levels. In TFC cultures exposed to TSH, the level of [methyl-3H]thymidine incorporation attained at a dose of 1 U TSH/1 was enhanced in the presence of TGF-β1 antiserum, although the similar stimulatory effect of 8-bromo cAMP was unaffected. Treatment of TFCs with phorbol 12-myristate 13-acetate (8 nmol/l) to activate protein kinase C (PKC) led to an enhanced incorporation of [methyl-3H]thymidine which was increased further after neutralisation of endogenous TGF-β1. While confirming, therefore, a role for autocrine TGF-β1 in maintaining control of TFC DNA synthesis in vitro, these findings provide evidence that an increase in the availability of autocrine TGF-β1 effected by EGF and TSH may play an instrumental role in limiting the cellular hyperplasia induced by these factors within the thyroid follicular microenvironment. Moreover, the present data also suggest that the availability of active autocrine TGF-β1 to TFCs under such conditions may be dependent upon a PKC-mediated mechanism. Journal of Endocrinology (1996) 148, 87–94


1991 ◽  
Vol 174 (5) ◽  
pp. 1147-1157 ◽  
Author(s):  
P T Le ◽  
S Lazorick ◽  
L P Whichard ◽  
B F Haynes ◽  
K H Singer

Human thymic epithelial (TE) cells produce interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6, cytokines that are important for thymocyte proliferation. The mRNAs for these cytokines are short-lived and are inducible by multiple stimuli. Thus, the steady-state levels for IL-1 and IL-6 mRNAs are critical in establishing the final cytokine protein levels. In this study we have evaluated the effect of epidermal growth factor (EGF), a growth factor for TE cells, and its homologue transforming growth factor alpha (TGF-alpha), on primary cultures of normal human TE cells for the levels of IL-1 alpha, IL-1 beta, IL-6, and TGF-alpha mRNA. We showed that TE cells expressed EGF receptors (EGF-R) in vitro and in vivo, and that treatment of TE cells with EGF or TGF-alpha increased IL-1 and IL-6 biological activity and mRNA levels for IL-1 alpha, IL-1 beta, and IL-6. Neither EGF nor TGF-alpha increased transcription rates of IL-1 alpha, IL-1 beta, and IL-6 genes, but rather both EGF and TGF-alpha increased cytokine mRNA stability. By indirect immunofluorescence assay, TGF-alpha was localized in medullary TE cells and thymic Hassall's bodies while EGF-R was localized to TE cells throughout the thymus. Thus, TGF-alpha and EGF are critical regulatory molecules for production of TE cell-derived cytokines within the thymus and may function as key modulators of human T cell development in vivo.


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