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.

Hepatocyte growth factor, keratinocyte growth factor, their receptors, fibroblast growth factor receptor-2, and the cells of the cornea.

Abstract: Purpose. The purpose of this study was to determine whether messenger RNA coding for hepatocyte growth factor (HGF), HGF receptor (MET), keratinocyte growth factor (KGF), KGH receptor, and fibroblast growth factor (FGF) receptor-2 were produced in primary cultures of human corneal epithelial, stromal fibroblast, and endothelial celss, as well as ex vivo corneal epithelium, endothelial cells transfected with the SV40 large T antigen, and control embryonic lung fibroblasts. The effects of exogenous HGF and KGF, compared to epidermal growth factor, on the proliferation of first passage corneal cells were also examined

Feedback mechanisms promote cooperativity for small molecule inhibitors of epidermal and insulin-like growth factor receptors.

Abstract: Epidermal growth factor receptor (EGFR) and insulin-like growth factor-I receptor (IGF-IR) can cooperate to regulate tumor growth and survival, and synergistic growth inhibition has been reported for combined blockade of EGFR and IGF-IR. However, in preclinical models, only a subset of tumors exhibit high sensitivity to this combination, highlighting the potential need for patient selection to optimize clinical efficacy. Herein, we have characterized the molecular basis for cooperative growth inhibition upon dual EGFR and IGF-IR blockade and provide biomarkers that seem to differentiate response. We find for epithelial, but not for mesenchymal-like, tumor cells that Akt is controlled cooperatively by EGFR and IGF-IR. This correlates with synergistic apoptosis and growth inhibition in vitro and growth regression in vivo upon combined blockade of both receptors. We identified two molecular aspects contributing to synergy: (a) inhibition of EGFR or IGF-IR individually promotes activation of the reciprocal receptor; (b) inhibition of EGFR-directed mitogen-activated protein kinase (MAPK) shifts regulation of Akt from EGFR toward IGF-IR. Targeting the MAPK pathway through downstream MAPK/extracellular signal-regulated kinase kinase (MEK) antagonism similarly promoted IGF-driven pAkt and synergism with IGF-IR inhibition. Mechanistically, we find that inhibition of the MAPK pathway circumvents a negative feedback loop imposed on the IGF-IR- insulin receptor substrate 1 (IRS-1) signaling complex, a molecular scenario that parallels the negative feedback loop between mTOR-p70S6K and IRS-1 that mediates rapamycin-directed IGF-IR signaling. Collectively, these data show that resistance to inhibition of MEK, mTOR, and EGFR is associated with enhanced IGF-IR-directed Akt signaling, where all affect feedback loops converging at the level of IRS-1.

Growth factors in inflammatory bowel disease.

Abstract: The pathogenesis of both ulcerative colitis and Crohn's disease is unknown but these forms of inflammatory bowel disease (IBD) may be associated with an inability of the intestinal mucosa to protect itself from luminal challenges and/or inappropriate repair following intestinal injury. Numerous cell populations regulate these broad processes through the expression of a complex array of peptides and other agents. Growth factors can be distinguished by their actions regulating cell proliferation. These factors also mediate processes such as extracellular matrix formation, cell migration and differentiation, immune regulation, and tissue remodeling. Several families of growth factors may play an important role in IBD including: epidermal growth factor family (EGF) [transforming growth factor alpha (TGF alpha), EGF itself, and others], the transforming growth factor beta (TGF beta) super family, insulin-like growth factors (IGF), fibroblast growth factors (FGF), hepatocyte growth factor (HGF), trefoil factors, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and others. Collectively these families may determine susceptibility of IBD mucosa to injury and facilitate tissue repair.

Epidermal growth factor rapidly stimulates prolactin gene transcription

Abstract: Epidermal growth factor (EGF) was originally characterized as a growth factor for various cell types1,2 and was subsequently shown to affect a number of cellular and molecular processes3,4, of which many might be considered as a part of the pleiotropic growth response (enhanced uptake of glucose, uridine and amino acids and stimulated synthesis of protein, RNA and DNA). Very early responses to EGF, such as increased sodium fluxes5 and stimulation of tyrosine phosphorylation6, have been proposed to mediate some or all of EGF's effects. In a number of tissues, EGF has been shown to increase the synthesis of specific proteins7-10. We have investigated the effects of EGF on prolactin synthesis in the GH4 rat pituitary cell line to gain further insight into the mechanism of EGF's actions on cellular functions. Addition of EGF to GH4 cells results in a three- to sixfold stimulation of prolactin synthesis, as well as a partial inhibition of cell growth7,8. In this report, we demonstrate that the increased prolactin synthesis appears to be the result of a rapid stimulation of prolactin gene transcription by EGF. It is tempting to speculate that very early transcription by EGF. It is tempting to speculate that very early transcriptional effects on specific genes, such as reported here in te case of the prolactin gene in GH4 cells, may mediate some or all of the later effects of EGF on cell cycle regulation in those cells for which it serves as a growth factor.