Yi-Ling Lin1, Hsiao-Ling Chen2, Shao-Bin Cheng3, Dah-Cherng Yeh4, Chu-Chun Huang4, Fang-Ku P'eng5, Tung-Chou Tsai6, Cheng-Chung Wu7, Chuan-Mu Chen8. 1. Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing UniversityTaichung 402, Taiwan; Department of General Surgery, Taichung Veterans General HospitalTaichung 407, Taiwan. 2. Department of Bioresources, Da-Yeh University Changhwa 515, Taiwan. 3. Department of General Surgery, Taichung Veterans General HospitalTaichung 407, Taiwan; School of Medicine, Chung-Shan Medical UniversityTaichung 402, Taiwan. 4. Department of General Surgery, Taichung Veterans General Hospital Taichung 407, Taiwan. 5. Department of Surgery, Faculty of Medicine, National Yang-Ming University Taipei 112, Taiwan. 6. Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University Taichung 402, Taiwan. 7. Department of General Surgery, Taichung Veterans General HospitalTaichung 407, Taiwan; Department of Surgery, Faculty of Medicine, National Yang-Ming UniversityTaipei 112, Taiwan; Department of Surgery, Chung-Shan Medical UniversityTaichung 402, Taiwan; Department of Surgery, Taipei Medical UniversityTaipei 110, Taiwan. 8. Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing UniversityTaichung 402, Taiwan; Rong-Hsing Translational Medicine Center, and iEGG Center, National Chung Hsing UniversityTaichung 402, Taiwan.
Abstract
INTRODUCTION: Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator. We firstly identified RCC1 gene hypermethylation in gastric tumor tissues using the differential methylation hybridization (DMH) microarray, but the role of RCC1 in the pathogenesis of gastric carcinoma is largely unknown. METHODS: Three gastric cancer cell lines (AGS, MKN45, and TSGH9201) were used to analyze RCC1 gene methylation, mRNA and protein expressions. Furthermore, 85 pairs of matched human gastric carcinoma samples in a tissue microarray were used to analyze RCC1 expression by immunohistochemistry staining. RESULTS: A differential methylation pattern was found in TSGH9201 (100%), MKN45 (87%), and AGS (62%) cell lines at the 9th CpG site of RCC1 exon 1. RCC1 mRNA and protein expressions in AGS cells were significantly higher than in TSGH9201 and MKN45 cell lines (P < 0.05). Tissue array data showed that RCC1 expression was detected in 21% (18/85) of gastric carcinoma tissues and in 80% (76/95) of adjacent non-tumor tissues. The expression of RCC1 in gastric carcinoma tissues was significantly lower than in adjacent non-tumor tissues (P < 0.001). Furthermore, an association between RCC1 expression and clinicopathological features showed that RCC1 expression was closely correlated with tumor differentiation and depth of invasion (P < 0.05). CONCLUSIONS: Our data indicate that RCC1 expression is frequently lost in poorly differentiated gastric cell lines and gastric carcinoma tissues. Loss of RCC1 expression is correlated with tumor differentiation and depth of invasion. These findings suggest that RCC1 may play a tumor suppressor role in gastric carcinoma.
INTRODUCTION:Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator. We firstly identified RCC1 gene hypermethylation in gastric tumor tissues using the differential methylation hybridization (DMH) microarray, but the role of RCC1 in the pathogenesis of gastric carcinoma is largely unknown. METHODS: Three gastric cancer cell lines (AGS, MKN45, and TSGH9201) were used to analyze RCC1 gene methylation, mRNA and protein expressions. Furthermore, 85 pairs of matched humangastric carcinoma samples in a tissue microarray were used to analyze RCC1 expression by immunohistochemistry staining. RESULTS: A differential methylation pattern was found in TSGH9201 (100%), MKN45 (87%), and AGS (62%) cell lines at the 9th CpG site of RCC1 exon 1. RCC1 mRNA and protein expressions in AGS cells were significantly higher than in TSGH9201 and MKN45 cell lines (P < 0.05). Tissue array data showed that RCC1 expression was detected in 21% (18/85) of gastric carcinoma tissues and in 80% (76/95) of adjacent non-tumor tissues. The expression of RCC1 in gastric carcinoma tissues was significantly lower than in adjacent non-tumor tissues (P < 0.001). Furthermore, an association between RCC1 expression and clinicopathological features showed that RCC1 expression was closely correlated with tumor differentiation and depth of invasion (P < 0.05). CONCLUSIONS: Our data indicate that RCC1 expression is frequently lost in poorly differentiated gastric cell lines and gastric carcinoma tissues. Loss of RCC1 expression is correlated with tumor differentiation and depth of invasion. These findings suggest that RCC1 may play a tumor suppressor role in gastric carcinoma.
Authors: J Richter; U Wagner; J Kononen; A Fijan; J Bruderer; U Schmid; D Ackermann; R Maurer; G Alund; H Knönagel; M Rist; K Wilber; M Anabitarte; F Hering; T Hardmeier; A Schönenberger; R Flury; P Jäger; J L Fehr; P Schraml; H Moch; M J Mihatsch; T Gasser; O P Kallioniemi; G Sauter Journal: Am J Pathol Date: 2000-09 Impact factor: 4.307
Authors: H Nishitani; M Ohtsubo; K Yamashita; H Iida; J Pines; H Yasudo; Y Shibata; T Hunter; T Nishimoto Journal: EMBO J Date: 1991-06 Impact factor: 11.598