Growth factor receptor inhibitor

About: Growth factor receptor inhibitor is a research topic. Over the lifetime, 4730 publications have been published within this topic receiving 297500 citations.

S100A11, an Dual Mediator for Growth Regulation of Human Keratinocytes

Abstract: We previously revealed a novel signal pathway involving S100A11 for inhibition of the growth of normal human keratinocytes (NHK) caused by high Ca++ or transforming growth factor β. Exposure to eit...

Down-regulation by growth factors of vascular smooth muscle angiotensin receptor gene expression.

Abstract: The effects of epidermal growth factor, basic fibroblast growth factor, and platelet-derived growth factor-BB on angiotensin type 1 (AT1) receptor gene expression were examined in rat thoracic aorta vascular smooth muscle cells (VSMC) in culture. Incubation of serum-deprived VSMC with 20 ng/ml epidermal growth factor, 20 ng/ml basic fibroblast growth factor, or 50 ng/ml platelet-derived growth factor-BB reduces AT1 receptor mRNA levels, as assessed by Northern hybridization analysis, to approximately 30% of control levels. This effect is maximal 4 hr after addition of each growth factor to the culture medium and is sustained for up to 24 hr of incubation after a single dose. There is a correlative loss of membrane-associated AT1 receptors and angiotensin II-stimulated inositol phosphate production after 24 hr of growth factor treatment. The half-life of AT1 receptor mRNA is reduced significantly by growth factors, compared with that for cells treated with actinomycin D alone to block transcription. This suggests that growth factors activate a mechanism that involves post-transcriptional destabilization of AT1 receptor mRNA. This effect can be blocked by prior treatment of VSMC with actinomycin D or cycloheximide, suggesting that the effect of the growth factors on AT1 receptor gene expression is mediated through induction of an unknown gene or genes that function to destabilize AT1 receptor mRNA and that mRNA translation is essential for the destabilizing effect. Nuclear run-on assays reveal that the growth factors also significantly reduce the rate of de novo AT1 receptor gene transcription. Thus, down-regulation of AT1 receptor gene expression by growth factors also appears to involve mechanisms that decrease the rate of AT1 receptor gene transcription. These data reveal marked down-regulation of AT1 receptor gene expression in VSMC by growth factor receptor activation, through mechanisms that involve both attenuation of transcription and post-transcriptional mRNA destabilization.

Crosstalk between EGFR and Extranuclear Steroid Receptors

Abstract: Epidermal growth factor (EGF) stimulates DNA synthesis and cytoskeletal rearrangement in human breast cancer (MCF-7) and human prostate cancer (LNCaP) cells. Both effects are inhibited by estrogen (ICI 182,780) and androgen (Casodex) antagonists. This supports the view that crosstalk exists between EGF and estradiol (ER) and androgen (AR) receptors and suggests that these receptors are directly involved in the EGF action. Our recent work shows that EGF stimulates ER phosphorylation on tyrosine and promotes the association of a complex between EGFR, AR/ER, and the kinase Src. The complex assembly triggers Src activity, epidermal growth factor receptor (EGFR) phosphorylation on tyrosine, and the EGF-dependent signaling pathway activation. In these cells, the AR/ER/Src complex is required for the EGF action, as the growth factor effects are abolished upon receptor silencing by specific SiRNAs and steroid antagonists or Src inhibition by the kinase inhibitor PP2.

The Effects of Transforming Growth Factor-β on Growth and Differentiation of the Continuous Rat Thyroid Follicular Cell Line, FRTL-5

Abstract: Transforming growth factor-β (TGFβ) has been shown to influence the growth and differentiation of many widely varied cell types in vitro, including some that are endocrinologically active. We have investigated the previously unknown effects of this unique growth factor in the differentiated rat thyroid follicular cell line FRTL-5. The cells demonstrated specific, high affinity binding of TGFβ, and as with other epithelial cells, the growth of these thyroid follicular cells was potently inhibited by addition of TGFβ to the culture medium. TGFβ caused a significant reduction in TSH-sensitive adenylate cyclase activity in the cells. The addition of (Bu)2cAMP along with the growth factor to cultures partially reversed the characteristic morphological changes seen with TGFβ, but did not reverse the growth inhibition. To further investigate the possible mechanisms of the effects of TGFβ on the cells, we measured the influence of the growth factor on [125I]TSH binding. TGFβ did not compete for specific TSH-bindi...