SMAD4, a key regulator of transforming growth factor-β (TGF-β) signaling, plays a major role in cell growth, migration, and apoptosis. In particular, TGF-β/SMAD induces growth arrest, and SMAD4 induces the expression of target genes such as p21WAF1 and p15INK4b through its interaction with several cofactors. Thus, inactivating mutations or the homozygous deletion of SMAD4 could be related to tumorigenesis or malignancy progression. However, in some cancer types, SMAD4 is neither mutated nor deleted. In the current study, we demonstrate that TGF-β signaling with a preserved SMAD4 function can contribute to cancer through associations with negative pathway regulators. We found that nuclear respiratory factor-1 (NRF1) is a novel interaction SMAD4 partner that inhibits TGF-β/SMAD4-induced p15INK4b mRNA expression by binding to SMAD4. Furthermore, we confirmed that NRF1 directly binds to the core region of the SMAD4 promoter, thereby decreasing SMAD4 mRNA expression. On the whole, our data suggest that NRF1 is a negative regulator of SMAD4 and can interfere with TGF-β/SMAD-induced tumor suppression. Our findings provide a novel perception into the molecular basis of TGF-β/SMAD4-signaling suppression in tumorigenesis.

Abstract:The discovery of a more cytotoxic macrosphelide derivative, including its total synthesis and bioassay are described. Application of the Koide protocol to a readily available propagylic alcohol allowed the rapid and practical synthesis of a macrosphelide A skeleton. This strategy enabled the successful improvement of the cytotoxic activity of the macrosphelide derivative.

In this study, the contactless measurement method with a optical displacement sensor(ODS, ADNS 9500) was proposed to overcome flaws in a rotary encoder based measurement under particular circumstances, such as a slippage and a case of little rotational inertia. The performance tests of the optical displacement sensor using data acquisition board and National Instruments's LabVIEW program were performed to accomplish accurate displacement measurements and the performance characteristics according to measurement direction, speed, acceleration, height and surface types were discovered through the repetitive tests. The experimental results indicate that, in order to get an accurate in-plane motion, the height(distance between the ODS and the target surface) has to be maintained at the range of 2.4 mm to 3.2 mm and the sensitivity(resolution) should be modified and applied to the formulae for displacement calculation, considering its measurement direction, speed and surface type.키워드 : 광 변위센서, 광 마우스 센서, 비접촉식 변위 측정, 민감도

Specificity protein 1 (SP1) is a DNA-binding protein that activates and regulates the transcription of multiple genes. Since aberrant expression of SP1 was known to be related to cancer development and progression, we focused on SP1 expression in gastric cancer and its correlation with disease outcomes. We discovered a different relationship between SP1 expression and patient survival in intestinal and diffuse-type gastric cancer. In diffuse-type gastric cancer, patient survival decreased as SP1 expression increased (P < 0.05) in accordance with previously published papers, whereas the lack of SP1 expression in intestinal-type gastric cancer was correlated significantly with poor survival (P < 0.05). Multivariate analysis demonstrated that SP1 downregulation is an independent negative prognostic factor in intestinal-type gastric cancer. When SP1 downreguation was forced in high SP1 expressor intestinal-type gastric cell line MKN28 with siRNA, both migration and invasion was increased but cell proliferation was decreased. In accordance with these results, microarray data in siRNA-transfected MKN28 showed that genes inhibiting migration were downregulated and the expression of genes negatively facilitating proliferation was increased. Both migration and invasion, however, in low SP1 expressor intestinal-type gastric cell line AGS was decreased by SP1 induction. In contrast to intestinal-type, in diffuse-type gastric cell line SNU484, high SP1 expressor, both migration and invasion were decreased by siRNA. Contrary to previous studies, which did not reflect differences between the 2 histological types, our results showed that weak SP1 expression is involved in cancer progression and metastasis, and leads to poor prognosis in intestinal-type gastric adenocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-112. doi:10.1158/1538-7445.AM2011-LB-112

No abstract