Loss of TGF-b type II receptor (TbRII, encoded by Tgfbr2) expression in the prostate stroma contributes to prostate cancer initiation, progression, and invasion.We evaluated whether TbRII loss also affected prostate cancer bone metastatic growth. Immunohistologic analysis revealed that TbRII expression was lost in cancer-associated fibroblasts in human prostate cancer bone metastatic tissues. W...

PURPOSE Transforming growth factor beta receptor II (TGFBR2) gene mutations are associated with Marfan syndrome; however, the relationship between the mutations and clinical phenotypes are not clear. METHODS Genomic DNA from peripheral blood leukocytes of a Chinese proband with Marfan syndrome, five of the proband's relatives, and 100 unrelated Chinese control subjects were isolated and scree...

BACKGROUND A new diagnostic and prognostic biomarker may be of value in cancer diseases. Our study aimed to evaluate the CDKN1A/p21 and TGFBR2 level measurable in a cohort of patients with breast cancer after mastectomy, and to confirm their suitability to serve as prognostic biomarkers of the cancer. METHODS The expression levels of CDKN1A/p21 and TGFBR2 were detected by reverse transcriptio...

BACKGROUND Mononucleotide tracts in the coding regions of the TGFBR2 and BAX genes are commonly mutated in microsatellite instability-high (MSI-high) colon cancers. The receptor TGFBR2 plays an important role in the TGFB1 (transforming growth factor-β, TGF-β) signaling pathway, and BAX plays a key role in apoptosis. However, a role of TGFBR2 or BAX mononucleotide mutation in colorectal cancer a...

Microsatellite instability promotes colonic tumorigenesis through generating frameshift mutations at coding microsatellites of tumor suppressor genes, such as TGFBR2 and ACVR2. As a consequence, signaling through these TGFbeta family receptors is abrogated in DNA Mismatch repair (MMR)-deficient tumors. How these mutations occur in real time and mutational rates of these human coding sequences h...

BACKGROUND AND AIMS Autoimmune pancreatitis (AIP) is a poorly understood human disease affecting the exocrine pancreas. The goal of the present study was to elucidate the pathogenic mechanisms underlying pancreatic autoimmunity in a murine disease model. METHODS A transgenic mouse with an S100A4/fibroblast-specific protein 1 (FSP1) Cre-mediated conditional knockout of the transforming growth ...

Although inactivating frameshift mutations in the Transforming growth factor beta receptor type 2 (TGFBR2) gene are considered as drivers of microsatellite unstable (MSI) colorectal tumorigenesis, consequential alterations of the downstream target proteome are not resolved completely. Applying a click-it chemistry protein labeling approach combined with mass spectrometry in a MSI colorectal can...

Recent work with mouse models of prostate cancer (CaP) has shown that inactivation of TGFβ signaling in prostate epithelium can cooperate with deletion of the Pten tumor suppressor to drive locally aggressive cancer and metastatic disease. Here, we show that inactivating the TGFβ pathway by deleting the gene encoding the TGFβ type II receptor (Tgfbr2) in combination with a deletion of the Apc t...

Genetic alterations in the TGFβ signaling pathway in combination with oncogenic alterations lead to cancer development in the intestines. However, the mechanisms of TGFβ signaling suppression in malignant progression of intestinal tumors have not yet been fully understood. We have examined Apc(Δ716) Tgfbr2(ΔIEC) compound mutant mice that carry mutations in Apc and Tgfbr2 genes in the intestinal...

Abstract The advent of immunotherapy has transformed our approach to cancer treatment; however, it is virtually ineffective in glioblastoma (GBM), the most common & malignant brain adults, due part inherently immunosuppressive tumor microenvironment (TME). Recent research identified GBM stem cells (GSCs) as key modulators TME, mainly through activation and recruitment pro-tumor immune (e.g....