TGFBR2 frameshift mutation in gastric tumors with microsatellite instability

Song, Jae-Hwi,Lee, Hwa-Sung,Yoon, Jung-Hwan,Kang, Young-Hwi,Nam, Suk-Woo,Lee, Jung-Young,Park, Won-Sang The Korean Society of Toxicogenomics and Toxicopro 2010 Molecular & cellular toxicology Vol.6 No.3

Microsatellite instability (MSI) is a form of genetic instability present in virtually all tumors from patients with hereditary nonpolyposis colon cancer and a subset of various sporadic tumors, including colorectal and gastric cancers. Transforming growth factor-beta receptor 2 (TGFBR2) mutations in MSI-positive cancer cell lines may partially inactivate TGF-$\beta$-induced growth inhibition. The aim of this study was to investigate whether MSI and TGFBR2 gene mutations contribute to the progression from gastric adenoma to cancer in multi step gastric carcinogenesis. MSIs were analyzed using 5 micro satellite markers and a frame shift mutation in poly(A)10 within the TGFBR2 gene in 50 gastric adenomas and 88 gastric cancer specimens. One (2.0%) of 50 gastric adenomas and 22 (25.0%) of 88 gastric cancers were MSI-positive. TGFBR2 frame shift mutations were found in 9 gastric cancers, but not in adenoma. All cases with the TGFBR2 frameshift mutation showed high-frequency MSIs. These results suggest that MSIs may occur in the development of gastric cancers, but not in adenomas less than 2 cm, and the TGFBR2 gene may be a target of genomic instability in MSI gastric carcinogenesis.

Polymorphisms of TGFBR2 contribute to the progression of papillary thyroid carcinoma

최봉근,김수강,박해정,박현경,권기환,임성훈,임성빈 대한독성 유전단백체 학회 2012 Molecular & cellular toxicology Vol.8 No.1

Transforming growth factor, beta receptor II (70/80 kDa) (TGFBR2) is a tumor suppressor. Mutations in the TGFBR2 gene appear to have an increased risk of developing several cancers. To investigate whether TGFBR2 polymorphisms are associated with the development of papillary thyroid carcinoma (PTC),three single nucleotide polymorphisms (SNPs) of TGFBR2 (rs764522, -1444C/G; rs3087465, -834G/A;rs2228048, Asn389Asn) were selected and genotyped by direct sequencing in 92 PTC patients and 330 control subjects. We also assessed the relationships between three SNPs of TGFBR2 and clinicopathologic characteristics of PTC such as size (⁄1 cm and ›1cm), number (unifocality and multifocality), location (one lobe and both lobe), extrathyroidal invasion, and lymph node metastasis. SNPStats and Haploview version 4.2 were used to analyze genetic data. Multiple logistic regression models (codominant1, codominant2,dominant, recessive, overdominant, and log-additive)were performed to calculate odds ratios (ORs), 95%confidence intervals (CIs), and P values. The three examined SNPs were not associated with PTC. In clinicopathologic characteristics, two promoter SNPs (rs3087465 and rs764522) were associated with lymph node metastasis (rs3087465, P=0.009 in the codominant1model, P=0.043 in the dominant model, P=0.003 in the overdominant model; rs764522, P=0.021in the codominant1 model, P=0.044 in the dominant model, P=0.016 in the overdominant model). The synonymous SNP rs2228048 was associated with extrathyroidal invasion (P=0.024 in the dominant model,P=0.015 in the log-additive model). The allele frequency of rs2228048 was significantly different between PTC with extrathyroidal invasion and PTC without extrathyroidal invasion (P=0.018, OR=0.46, 95% CI=0.24-0.88). These results suggest that TGFBR2 may be associated with the progression of PTC in Korean population.

Association between the TGFBR2 G-875A Polymorphism and Cancer Risk: Evidence from a Meta-analysis

Huang, Yong-Sheng,Zhong, Yu,Yu, Long,Wang, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Disrupted transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling is involved in the development of various types of cancer and the TGF-${\beta}$ receptor II (TGFBR2) is a key mediator of TGF-${\beta}$ growth inhibitory signals. It is reported that the G-875A polymorphism in TGFBR2 is implicated in risk of various cancers. However, results for the association between this polymorphism and cancer remain conflicting. To derive a more precise estimation, a meta-analysis of 3,808 cases and 4,489 controls from nine published case-control studies was performed. Our analysis indicated that G-875A is associated with a trend of decreased cancer risk for allele A versus(vs.) allele G [odds ratio (OR) =0.64, 95% confidence intervals (CI): 0.55-0.74], as well as for both dominant model [(A/A+G/A) vs. G/G, OR=0.76, 95% CI: 0.64-0.90] and recessive model [A/A vs. (G/G+G/A), OR=0.74, 95% CI: 0.59-0.93). However, larger scale primary studies are required to further evaluate the interaction of TGFBR2 G-875A polymorphism and cancer risk in specific cancer subtypes.

Effect of Different Ingredients in Traditional Korean Medicine for Human Uterine Leiomyoma on Normal Myometrial and Leiomyomal Smooth Muscle Cell Proliferation

Prati Bajracharya,이은주,이동목,Sang Hee Shim,김극준,Sung Ho Lee,Jei Jun Bae,전상식,Tae Kyun Lee,Seok Hoon Kwon,최인호 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.11

Crude water extracts of 13 traditional Korean medicinal ingredients used for leiomyomal treatment were prepared and used to treat human uterine normal myometrial and leiomyomal cell cultures. All the ingredients inhibited proliferation and altered the morphology of both myometrial and leiomyomal cells. Among the 13 ingredients, n-hexane-, chloroform-, and ethylacetate-soluble fractions were extracted from seven ingredients that potently inhibited cell proliferation in their water extract form. Among these, the ethylacetate-fraction of Phlomis umbrosa and Spatholobus suberectus, and the chloroform-fraction of Curcuma zedoaria and S. suberectus inhibited leiomyomal cell proliferation significantly compared to myometrial cell proliferation. Similarly, immunohistochemical analysis showed the inhibition of transforming growth factor-beta receptor 2 in leiomyomal tissue after treatment with the fractions of the ingredients. Moreover, the chloroform-fraction of C. zedoaria was subfractionated by open column chromatography. Two of the eight subfractions (fractions 6 and 7) potently inhibited cell proliferation in leiomyoma compared to myometrium. Further study will be performed with the goal of isolating specific compounds from two effective subfractions of C. zedoaria, ethylacetate-fraction of P. umbrosa, and the ethylacetate and chloroform-fractions of S. suberectus. The present study may be helpful in developing an alternative remedy to leiomyoma with minimal side-effects compared to the current treatments.

Tissue engineering a tendon-bone junction with biodegradable braided scaffolds

Harshini Ramakrishna,Tieshi Li,Ting He,Joseph Temple,Martin W. King,Anna Spagnoli 한국생체재료학회 2019 생체재료학회지 Vol.23 No.2

Background: Tendons play an important role in transferring stress between muscles and bones and in maintaining the stability of joints. Tendon tears are difficult to heal and are associated with high recurrence rates. So, the objective of this study was to develop a biodegradable scaffold for tendon-bone junction regeneration. Methods: Two types of polylactic acid (PLA) yarns, having fibers with round and four deep grooved cross-sections, were braided into tubular scaffolds and cultured with murine Transforming growth factor beta type II receptor (Tgfbr2)-expressing joint progenitor cells. The scaffolds were designed to mimic the mechanical, immuno-chemical and biological properties of natural mouse tendon-bone junctions. Three different tubular scaffolds measuring 2mm in diameter were braided on a Steeger 16-spindle braiding machine and biological and mechanical performance of the three scaffolds were evaluated. Results: The mechanical test results indicated that three different braided scaffold structures provided a wide range of mechanical properties that mimic the components of tendon bone junction and results of the biological tests confirmed cell viability, active cell attachment and proliferation throughout all three scaffolds. Conclusions: This study has identified that the three proposed types of braided scaffolds with some improvement in their structures have the potential to be used as scaffolds for the regeneration of a tendon bone tissue junction.