Smad4 is the common mediator of transforming growth factor-beta (TGF-beta) superfamily signaling, which functions in diverse developmental processes in mammals. To study the role of Smad4 in skin development, a keratinocyte-specific null mutant of Smad4 (Smad4(co/co);K5-Cre) was generated in mice using the Cre-loxP system. The Smad4-mutant mice exhibited progressive alopecia as a result of the ...

Inactivation of TGF-beta/SMAD4 signaling was postulated to play an important role in breast cancer development. Even though SMAD4 is located on 18q21, a region frequently lost in breast cancers, point mutations of SMAD4 were rarely observed, implying that biallelic inactivation of SMAD4 was not necessary in the process. In this study, a novel homozygous deletion of SMAD4 was identified in breas...

We investigated the role of Smad4, a signaling molecule of the TGF-beta pathway, in T cells on the pathology of Sjögren's syndrome (SS) in nonobese diabetic (NOD) mice, an animal model of SS. T cell-specific Smad4-deleted (Smad4fl/fl,CD4-Cre; Smad4 tKO) NOD mice had accelerated development of SS compared with wild-type (Smad4+/+,CD4-Cre; WT) NOD mice, including increased lymphocyte infiltration...

PURPOSE SMAD4 (also called Dpc4) is a tumor suppressor in the TGF-beta signaling pathway that is genetically inactivated in approximately 55% of all pancreatic adenocarcinomas. We investigated whether prognosis after surgical resection for invasive pancreatic adenocarcinoma is influenced by SMAD4 status. EXPERIMENTAL DESIGN Using immunohistochemistry, we characterized the SMAD4 protein status...

Smad4 loss occurs frequently in human skin squamous cell carcinoma (SCC), but it is unknown whether this loss increases UV-induced carcinogenesis, a major etiological factor in skin cancer. In the present study, mice with keratinocyte-specific Smad4 deletion (K14.Smad4(-/-)) and wild-type (WT) littermates were chronically UV-irradiated. Compared with WT, K14.Smad4(-/-) mice exhibited increased ...

Smad4 in partnership with R-Smads (receptor-regulated Smads) activates TGF-beta (transforming growth factor-beta)-dependent signalling pathways essential for early mouse development. Smad4 null embryos die shortly after implantation due to severe defects in cell proliferation and visceral endoderm differentiation. In the basal state, Smad4 undergoes continuous shuttling between the cytoplasm an...

Loss of chromosome 18q21 is well documented in colorectal cancer, and it has been suggested that this loss targets the DCC, DPC4/SMAD4, and SMAD2 genes. Recently, the importance of SMAD4, a downstream regulator in the TGF-beta signaling pathway, in colorectal cancer has been highlighted, although the frequency of SMAD4 mutations appears much lower than that of 18q21 loss. We set out to investig...

PURPOSE Mothers against decapentaplegic homologue 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study is to more precisely characterize its role in the development and progression of human gastric carcinoma. EXPERIMENTAL DESIGN The expression of SMAD4 was investigated in 283 gastric adenocarcinomas and related lesions, as well as ...

Smad4 has recently been identified as a tumor suppressor gene in a variety of cancers, yet the role of Smad4 in renal cell carcinoma (RCC) remained to be elusive. Therefore, the aim of the present study was to explore the function of Smad4 in RCC. The expression of Smad4 reduced the growth rate of RCC. The levels of Smad4 and forkhead box protein H1 (FOXH1) mRNA were reduced, while the levels o...

This study investigated the oncologic impact of loss of SMAD4 expression in resected left-sided pancreatic cancer and its correlation with tumor metabolism.From 2005 to 2011, the medical records of patients who underwent radical distal pancreatectomy for resectable pancreatic cancer were retrospectively reviewed. Formalin-fixed, paraffin embedded tissue from 32 patients was investigated. Clinic...