aim : in this study, to clarify the smad4blocking impact on fibrosis process, we investigated its down-regulation by shrna on activated human lx-2 cell, in vitro.   background : liver fibrosis is a critical consequence of chronic damage to the liver that can progress toward advanced diseases, liver cirrhosis and hepatocellular carcinoma (hcc).  different smad proteins play as major mediators in...

objective: infection with herpes simplex virus type 1 induces viral latency in neuron trigeminal ganglions. the late associated transcript (lat) is uniquely expressed in infected neural cells, however no coding protein associated with these transcripts has been identified in infected cells. it has been shown that six micrornas transcribed from lat have the capabilities to affect the cell signal...

Purposes SMAD4/DPC4 mutations have been associated with aggressive behavior in pancreatic ductal adenocarcinomas (PDAC), and it has recently been suggested that RUNX3 expression combined with SMAD4 status may predict the metastatic potential of PDACs. We evaluated the prognostic utility of SMAD4/RUNX3 status in human PDACs by immunohistochemistry. Materials and Methods Immunohistochemical sta...

UNLABELLED SMAD4 has been suggested to inhibit the activity of the WNT/β-catenin signaling pathway in cancer. However, the mechanism by which SMAD4 antagonizes WNT/β-catenin signaling in cancer remains largely unknown. Aurora A kinase (AURKA), which is frequently overexpressed in cancer, increases the transcriptional activity of β-catenin/T-cell factor (TCF) complex by stabilizing β-catenin thr...

The bone morphogenetic proteins (BMPs) Smad4 and Id2 exert their effect on colorectal carcinoma via several uncharacterized mechanisms. In this study, we investigated whether the transcription factor Id2, which has been implicated in colorectal carcinoma proliferation and metastasis, is involved in BMP-7/Smad4 signaling, or whether it is regulated by BMP-7 via another mechanism in this cell typ...

BACKGROUND Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma. METHODS Combined expression patterns based on Smad4+/- and PTEN+/- status were evaluated by immunostaining us...

Smad4 is a critical regulator of transforming growth factor (TGF)-β signaling and is defective in numerous human cancers. In total, 30% of pancreatic cancers harbor a homozygous deletion of Smad4. The human pancreatic cancer cell line, BxPC3, has been reported to be Smad4-null due to a homozygous deletion and has been widely used as a Smad4-null model. The present study reports that Smad4 DNA i...

TGF-beta activates receptor-regulated Smad (R-Smad) through phosphorylation by type I receptors. Activated R-Smad binds to Smad4 and the complex translocates into the nucleus and stimulates the transcription of target genes through association with co-activators including p300. It is not clear, however, how activated Smad complexes are removed from target genes. In this study, we show that TGF-...

Smad4 plays a pivotal role in all transforming growth factor beta (TGF-beta) signaling pathways. Here we describe six widely expressed alternatively spliced variants of human Smad4 with deletions of different exons in the linker, the region of Smad4 that separates the two well-conserved MH1 and MH2 domains. All these Smad4 variants form complexes with activated Smad2 and Smad3 and are incorpora...

SMAD4 serves as a common mediator for signaling of TGF-β superfamily. Previous studies illustrated that SMAD4-null mice die at embryonic day 6.5 (E6.5) due to failure of mesoderm induction and extraembryonic defects; however, functions of SMAD4 in each germ layer remain elusive. To investigate this, we disrupted SMAD4 in the visceral endoderm and epiblast, respectively, using a Cre-loxP mediate...