The signalling pathways downstream of the transforming growth factor beta (TGFb) family of cytokines play critical roles in all aspects of cellular homeostasis. The phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) has been implicated in TGFb-induced epithelial-to-mesenchymal transition and apoptosis. The precise molecular mechanisms by which TGFb cytokines induce th...

Paracrine effect of transforming growth factorb 1 (TGFb 1) on autoimmune insulitis and diabetes was studied by transgenic production of the active form of porcine TGFb 1 (pTGFb 1) in pancreatic islet (islet) a cells in nonobese diabetic (NOD) mice under the control of rat glucagon promoter (RGP) (NOD-RGP-TGFb 1). None of 27 NOD-RGP-TGFb 1 mice developed diabetes by 45 wk of age, in contrast to ...

Objective: Restenosis following angioplasty involves processes that may be influenced by local production of cytokines. We investigated the expression of active and total transforming growth factor b (TGFb) following porcine coronary angioplasty (PTCA), and have correlated this with the expression of potential in vivo activators of TGFb: mannose-6-phosphate / insulin-like growth factor-II (M6P/...

Purpose: To determine whether inhibition of TGFb signaling prior to irradiation sensitizes human and murine cancer cells in vitro and in vivo. Experimental Design: TGFb-mediated growth and Smad phosphorylation of MCF7, Hs578T, MDAMB-231, and T47D human breast cancer cell lines were examined and correlated with clonogenic survival following graded radiation doses with and without pretreatment wi...

Purpose: To determine whether inhibition of TGFb signaling prior to irradiation sensitizes human and murine cancer cells in vitro and in vivo. Experimental Design: TGFb-mediated growth and Smad phosphorylation of MCF7, Hs578T, MDAMB-231, and T47D human breast cancer cell lines were examined and correlated with clonogenic survival following graded radiation doses with and without pretreatment wi...

ated, and in this configuration TGFb is unable to bind University of California, San Francisco to its receptors; that is, TGFb is latent. In most cases, San Francisco, California 94143-0854 the complex of LAP and TGFb (the small latent complex 5 Department of Medicine SLC) is joined by latent TGFb binding protein 1 (LTBP1), 6 Cell Biology and Kaplan Cancer Center a matrix protein with sequence ...

Lysophosphatidic acid (LPA) is a multifunctional intercellular phospholipid mediator present in blood and other biological fluids. In cancer cells, LPA stimulates expression or activity of inflammatory cytokines, angiogenic factors, matrix metalloproteinases, and other oncogenic proteins. In this study, we showed that LPA upregulated expression of the cyclin-dependent kinase inhibitor p21 in TG...

Transforming Growth Factor b (TGFb) is an immunosuppressive cytokine that inhibits pro-inflammatory functions of T cells, and is a major contributor to abrogating TH1 and cytotoxic T cell activity against tumors. While canonical signal transduction through effector Smads has been well-defined as a requirement for TGFb-mediated inhibition of T cells, essential non-canonical pathways have not, to...