We report that IL-17 significantly increases the secretion of CXCL1 and CXCL5 from mammary carcinoma cells, which is downregulated by TGF-β through the type II TGF-β receptor (TβRII). Carcinoma cells with conditional knockout of TβRII (Tgfbr2(KO)) have enhanced sensitivity to IL-17a in the stimulation of chemokine secretion. During polyoma middle T (PyMT) induced tumor progression, levels of Th...

objective: nowadays, cord blood hematopoietic stem cells (hscs) are known as a valuable source for bone marrow transplantation but unfortunately their insufficient number is a limiting factor for using them in adult bone marrow transplantation. cord blood hcss expansion is an approach to overcome this problem, by inducing their self-renewal. tgf-b signaling pathway is a key inhibitory agent for...

Transforming growth factor B (TGFB) plays a key role in maintaining tissue homeostasis by inducing cell cycle arrest, differentiation and apoptosis, and ensuring genomic integrity. Furthermore, TGFB orchestrates the response to tissue injury and mediates repair by inducing epithelial to mesenchymal transition and by stimulating cell motility and invasiveness. Although loss of the homeostatic ac...

Frameshift and nonsense mutations are common in tumors with microsatellite instability, and mRNAs from these mutated genes have premature termination codons (PTCs). Abnormal mRNAs containing PTCs are normally degraded by the nonsense-mediated mRNA decay (NMD) system. However, PTCs located within 50-55 nucleotides of the last exon-exon junction are not recognized by NMD (NMD-irrelevant), and som...

Transforming growth factor β1 (TGFB1) and transforming growth factor β type 2 receptor (TGFBR2) are key components of TGF-β signaling and play an important role in vascular remodeling in placentation. Several polymorphisms have been identified in TGFB1 and TGFBR2 genes, including those associated with the regulation of TGF-β1 levels and TGF binding to its receptor. The decrease of TGF-β1 levels...

Aberrant TGFbeta signaling is common in human cancers and contributes to tumor metastasis. Here, we demonstrate that Gr-1+CD11b+ myeloid cells are recruited into mammary carcinomas with type II TGF beta receptor gene (Tgfbr2) deletion and directly promote tumor metastasis. Gr-1+CD11b+ cells infiltrate into the invasive front of tumor tissues and facilitate tumor cell invasion and metastasis thr...

Marfan syndrome (MFS, MIM #154700) is an autosomal dominant disorder of the extra cellular matrix affecting the connective tissue with cardiovascular, skeletal, neurological, integumental and ocular abnormalities.1 More than 85% of MFS cases are causally linked to mutations in the fibrillin-1 gene (FBN1, 15q21.1). In 1994, a second locus (MFS2) (MIM #154705) was found to map at 3p25–p24.22 afte...

TGF-β is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-β functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2(MyeKO)) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2(MyeKO) bone marrow ...

Squamous cell carcinomas occurring at transition zones are highly malignant tumors with poor prognosis. The identity of the cell population and the signaling pathways involved in the progression of transition zone squamous cell carcinoma are poorly understood, hence representing limited options for targeted therapies. Here, we identify a highly tumorigenic cancer stem cell population in a mouse...

BACKGROUND Regulatory T-cell dysfunction is associated with development of the complex genetic conditions atopy and asthma. Therefore, we hypothesized that single nucleotide polymorphisms in genes involved in the development and function of regulatory T cells are associated with atopy and asthma development. OBJECTIVE To evaluate main effects and gene-gene interactions of haplotype tagging si...