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.

Production of transforming growth factor alpha in human pancreatic cancer cells: evidence for a superagonist autocrine cycle.

Abstract: Previous work showed that cultured human pancreatic cancer cells overexpress the epidermal growth factor (EGF) receptor. In the present study, we sought to determine whether some of these cell lines produce transforming growth factor alpha (TGF-alpha). Utilizing a radiolabeled TGF-alpha cDNA in hybridization experiments, we determined that ASPC-1, T3M4, PANC-1, COLO-357, and MIA PaCa-2 cell lines expressed TGF-alpha mRNA. Serum-free medium conditioned by T3M4 and ASPC-1 cells contained significant amounts of TGF-alpha protein. Although unlabeled TGF-alpha readily competed with 125I-labeled EGF for binding, each cell line exhibited lower surface binding and internalization of 125I-labeled TGF-alpha as compared to 125I-labeled EGF. Both TGF-alpha and EGF significantly enhanced the anchorage-independent growth of PANC-1, T3M4, and ASPC-1 cells. However, TGF-alpha was 10- to 100-fold more potent than EGF. These findings suggest that the concomitant overexpression of EGF receptors and production of TGF-alpha may represent an efficient mechanism for certain cancer cells to obtain a growth advantage.

Hyperactivation of MAPK Induces Loss of ERα Expression in Breast Cancer Cells

Abstract: ERα-negative breast tumors tend to overexpress growth factor receptors such as epidermal growth factor receptor or c-erbB-2 Raf-1 is a key intermediate in the signal transduction pathways of these receptors High levels of constitutive Raf kinase (Δraf) activity imparts ERα- positive MCF-7 breast cancer cells with the ability to grow in the absence of estrogen Δraf transfectants maintained in estrogen-depleted media showed greatly diminished responses to 17β-estradiol or the pure antiestrogen ICI 182,780 Western blotting, ligand binding, and immunohistochemistry assays revealed a loss of ERα protein expression, and ribonuclease protection assays indicated that this correlated with loss of ERα message In examining the basal expression of estrogen-induced genes in the stable transfectants or in transient cotransfection assays with an estrogen-response element- reporter construct and Δraf or constitutively active MAPK kinase (ΔMEK), no ligand- independent activation of ERα was observed Transient express

Skeletal Growth Factors

Abstract: Bone Cells and their Function Bone Matrix Biology of Growth Factors Mechanisms of Action of Skeletal Growth Factors in Osteoblasts In Vitro and In Vivo Models to Study Growth Factor Actions in Bone Insulin-like Growth Factors: Their Binding Proteins and Growth Regulation Insulin-like Growth Factors and the Skeleton Clinical Aspects of Insulin-like Growth Factors Biology of Platelet-Derived Growth Factor Platelet-Derived Growth Factor: Skeletal Actions and Regulation Fibroblast Growth Factors and their Receptors Fibroblast Growth Factors and Osteogenesis Fibroblast Growth Factors, Chondrogenesis, and Related Clinical Disorders Hepatocyte Growth Factor Transforming Growth Factor-B Transforming Growth Factor-B in Skeletal Development and Maintenance Activin and Follistatin Activin, Follistatin, and Bone Bone Morphogenetic Proteins Bone Morphogenetic Proteins and Skeletal and Nonskeletal Development Bone Morphogenetic Proteins and the Adult Skeleton The Role of Growth Factors in Fracture Healing Clinical Disorders Associated with Bone Morphogenetic Proteins Parathyroid Hormone-related Protein Role of Parathyroid Hormone-related Protein and Indian Hedgehog in Skeletal Development Osteoprotegerin Nonskeletal Effects of Cytokines Secreted by Bone Cells Colony-Stimulating Factors and Bone Role of Cytokines in Postmenopausal Osteoporosis Role of Cytokines in Osteopetrosis Cytokines, Growth Factors, and Malignancy Clinical Use of Growth Factors Use of Growth Factors for Osteoporotic Therapy Inde

PTGF-β, a type β transforming growth factor (TGF-β) superfamily member, is a p53 target gene that inhibits tumor cell growth via TGF-β signaling pathway

Abstract: Identification and characterization of p53 target genes would lead to a better understanding of p53 functions and p53-mediated signaling pathways. Two putative p53 binding sites were identified in the promoter of a gene encoding PTGF-β, a type β transforming growth factor (TGF-β) superfamily member. Gel shift assay showed that p53 bound to both sites. Luciferase-coupled transactivation assay revealed that the gene promoter was activated in a p53 dose- as well as p53 binding site-dependent manner by wild-type p53 but not by several p53 mutants. The p53 binding and transactivation of the PTGF-β promoter was enhanced by etoposide, a p53 activator, and was largely blocked by a dominant negative p53 mutant. Furthermore, expression of endogenous PTGF-β was remarkably induced by etoposide in p53-positive, but not in p53-negative, cell lines. Finally, the conditioned medium collected from PTGF-β-overexpressing cells, but not from the control cells, suppressed tumor cell growth. Growth suppression was not, however, seen in cells that lack functional TGF-β receptors or Smad4, suggesting that PTGF-β acts through the TGF-β signaling pathway. Thus, PTGF-β, a secretory protein, is a p53 target that could mediate p53-induced growth suppression in autocrinal as well as paracrinal fashions. The finding made a vertical connection between p53 and TGF-β signaling pathways in controlling cell growth and implied a potential important role of p53 in inflammation regulation via PTGF-β.