Microsatellite instability and mutated type II transforming growth factor-β receptor gene in gliomas

Izumoto, Shuichi; Arita, Norio; Ohnishi, Takanori; Hiraga, Shoju; Taki, Takuyu; Tomita, Naohiro; Ohue, Masayuki; Hayakawa, Tõru

doi:10.1016/s0304-3835(96)04583-1

Cited by 77 publications

(49 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These mutations are generated by insertion or deletion of adenines in a 10-bp polyadenine track, leading to expression of a truncated, inactive receptor product [78]. Similar mutations occur in MSI gastric tumors and gliomas [79]. Mutational inactivation of the TGFb type II receptor also occurs in a proportion of microsatellite-stable colorectal cancers.…”

Section: Tgfb Signaling As a Tumor Suppressor Pathwaymentioning

confidence: 99%

The logic of TGFβ signaling

2006

View full text Add to dashboard Cite

The identification of the TGFb cytokine signaling pathway, including membrane receptor serine/threonine kinases and Smad transcription factors as their substrates, has allowed the delineation of a process for conversion of these signals into programs of gene activation and repression that underlie critical cell fate and developmental decisions. The deconstruction of one of these responses -the cell cycle arrest response -into its elemental molecular parts has shed light into the mechanisms used by tumors to evade surveillance and cause metastasis.

show abstract

Section: Tgfb Signaling As a Tumor Suppressor Pathwaymentioning

confidence: 99%

The logic of TGFβ signaling

2006

View full text Add to dashboard Cite

show abstract

“…BAT-TbRII mutations are found in subsets of colon cancers, gastric cancers, and gliomas with microsatellite instability (Markowitz et al, 1995;Myeroff et al, 1995;Izumoto et al, 1997). However, Smad mutation has not been reported in GB.…”

Section: Tgf-b As the Tumor Suppressor And Glioblastomamentioning

confidence: 99%

TGF-β, Neuronal Stem Cells and Glioblastoma

Golestaneh

Mishra

2005

Oncogene

View full text Add to dashboard Cite

Transforming growth factor beta (TGF-b) signaling leads to a number of biological end points involving cell growth, differentiation, and morphogenesis. Typically, the cellular effect accompanies an induction of mesodermal cell fate and inhibition of neural cell differentiation. However, during pathological conditions, these defined effects of TGF-b can be reversed; for example, the growthinhibitory effect is replaced with its tumor promoting ability. A multitude of factors and cross-signaling pathways have been reported to be involved in modulating the dual effects of TGF-b. In this review, we focus on the potential role of TGF-b signal transduction during development of neural progenitor cells and its relation to glioblastoma development from neural stem cells.

show abstract

“…8 Mutations in the TGF-b superfamily genes have been found in various cancers. The TGF-b receptor II (TGFBR2) gene is frequently mutated in colon cancers, 9,10 gastric cancers, 10,11 and in gliomas 12 with microsatellite instability. SMAD4 mutations occur mainly in pancreatic cancers, in which the SMAD4 gene was first identified as a tumorsuppressor gene.…”

mentioning

confidence: 99%

Reduced transforming growth factor-β receptor II expression in hepatocellular carcinoma correlates with intrahepatic metastasis

Mamiya

Yamazaki

Masugi

et al. 2010

Laboratory Investigation

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) occurs mainly in the liver associated with chronic hepatitis and hepatic cirrhosis as a result of prolonged viral infection. Transforming growth factor-b (TGF-b) induces the fibrosis in hepatic cirrhosis, although it is also an inhibitor of hepatocyte proliferation. To understand the role of TGF-b signaling in HCC progression, we analyzed gene expression in HCC cells in relation to TGF-b signaling using a two-way clustering algorithm. By the analysis, five HCC cell lines were classified into two groups according to their metastatic capacity. TGF-b receptor II (TGFBR2) was downregulated in metastatic cells, which did not show a response to TGF-b. Immunohistochemistry demonstrated clear membrane distribution of TGFBR2 in noncancerous hepatocytes, whereas reduced TGFBR2 expression was observed in 34 of 136 HCCs. In clinical cases, reduced TGFBR2 expression correlated with larger tumor size (Po0.001), poor differentiation (Po0.001), portal vein invasion (P ¼ 0.002), intrahepatic metastasis (IM) (Po0.001), and shorter recurrence-free survival (P ¼ 0.022). In conclusion, reduced TGFBR2 expression was associated with aggressive features of HCC such as IM, and may represent an immunohistochemical biomarker to detect aggressive HCC. Hepatocellular carcinoma (HCC) is a common cause of death from cancer worldwide. 1 Prolonged infection with hepatitis virus often causes chronic hepatitis, followed by liver cirrhosis. 2 During the development of these liver diseases, transforming growth factor-b (TGF-b) has an important role in fibrosis of the lesions. 3 HCCs mainly occur in those injured livers with activated TGF-b signaling, although TGF-b inhibits hepatocyte cell growth in the normal liver. 4,5 TGF-b signaling is activated when a TGF-b ligand binds to its receptor on the cell membrane. The downstream effectors, SMAD2 and SMAD3, together with SMAD4, translocate to the nucleus and regulate the expression of various genes, including cyclin-dependent kinase inhibitor 1A (CDKN1A), which is involved in cell growth arrest. 6,7 TGF-b signaling is also suggested to be involved in the malignant progression of tumors. TGF-b can induce epithelial-mesenchymal transition and promote tumor cell invasion, and may also have angiogenic and immunosuppressive effects on the tumor microenvironment, all of which promote metastasis. 8 Mutations in the TGF-b superfamily genes have been found in various cancers. The TGF-b receptor II (TGFBR2) gene is frequently mutated in colon cancers, 9,10 gastric cancers, 10,11 and in gliomas 12 with microsatellite instability. SMAD4 mutations occur mainly in pancreatic cancers, in which the SMAD4 gene was first identified as a tumorsuppressor gene. 13 In HCCs, however, mutations in TGF-b superfamily genes are rare, 14,15 and alteration of TGF-b signaling is still unclear and controversial. To investigate alterations of TGF-b signaling in HCC progression, we compared the expression profiles of TGF-b signalingrelated genes in HCC cells exhibiting different metastatic potential. We...

show abstract

Microsatellite instability and mutated type II transforming growth factor-β receptor gene in gliomas

Cited by 77 publications

References 19 publications

The logic of TGFβ signaling

The logic of TGFβ signaling

TGF-β, Neuronal Stem Cells and Glioblastoma

Reduced transforming growth factor-β receptor II expression in hepatocellular carcinoma correlates with intrahepatic metastasis

Contact Info

Product

Resources

About