Increased Expression but Not Genetic Alteration of BRG1, a Component of the SWI/SNF Complex, Is Associated with the Advanced Stage of Human Gastric CarcinomasSentani K. · Oue N. · Kondo H. · Kuraoka K. · Motoshita J. · Ito R. · Yokozaki H. · Yasui W.
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
BRG1, a component of the SWI/SNF complex, regulates gene transcription through chromatin remodeling. Certain human cancer cell lines have been shown to contain homozygous deletions or mutations, half of which are concentrated in exons 4 and 10, resulting in aberrant BRG1 expression. We examined the expression of BRG1 in 38 gastric carcinomas and corresponding nonneoplastic mucosa by using the quantitative real-time RT-PCR method. Twenty-three carcinomas (61%) showed increased BRG1 expression in tumor tissue in comparison with that in nonneoplastic mucosa. The T/N ratio (the expression level of BRG1 mRNA in tumor tissues relative to those in corresponding nonneoplastic mucosa) in advanced cases of gastric carcinoma (stages III and IV) was significantly higher than that in cases of stage I and II carcinoma (p = 0.029). Furthermore, gastric carcinomas with lymph node metastasis showed a tendency to express BRG1 at a higher level than gastric carcinomas without metastasis (p = 0.097). We also searched for genetic alterations of the BRG1 gene in 8 gastric carcinoma cell lines and 33 primary gastric carcinomas by PCR-SSCP analysis. No SSCP variants in exons 4, 10 and 16 of the BRG1 gene were found in both gastric carcinoma cell lines and primary gastric carcinomas. These results suggest that, although genetic abnormality of BRG1 might be rare, an increased expression of BRG1 might be associated with the development and progression of gastric carcinoma.
© 2002 S. Karger AG, Basel
- Yasui W, Yokozaki H, Fujimoto J, Naka K, Kuniyasu H, Tahara E: Genetic and epigenetic alterations in multistep carcinogenesis of the stomach. J Gastroenterol 2000;35:111–115.
- Yasui W, Oue N, Kuniyasu H, Ito R, Tahara E, Yokozaki H: Molecular diagnosis of gastric cancer: Present and future. Gastric Cancer 2001;4:113–121.
- Grunstein M: Histone acetylation in chromatin structure and transcription. Nature 1997;389:349–352.
- Morales V, Richard-Foy H: Role of histone N-terminal tails and their acetylation in nucleosome dynamics. Mol Cell Biol 2000;20:7230–7237.
Ono S, Oue N, Kuniyasu H, Suzuki T, Ito R, Matsusaki K, Ishikawa T, Tahara E, Yasui W: Acetylated histone H4 is reduced in human gastric carcinomas. J Exp Clin Cancer Res, in press.
Wade PA, Wollfe AP: Transcriptional regulation: SWItching circuitry. Curr Biol 1999;9:221–224.
- Suzuki T, Yokozaki H, Kuniyasu H, Hayashi K, Naka K, Ono S, Ishikawa T, Tahara E, Yasui W: Effect of trichostatin A on cell growth and expression of cell cycle- and apoptosis-related molecules in human gastric and oral carcinoma cell lines. Int J Cancer 2000;88:992–997.
Kingston RE, Narlikar GJ: ATP-dependent remodeling and acetylation as regulator of chromatin fluidity. Genes Dev 1999;13:2335–2352.
- Phelan ML, Narlikar GJ, Kingston RE: Reconstitution of a core chromatin remodeling complexes from SWI/SNF subunits. Mol Cell 1999;3:247–253.
- Tyler JK, Kadonaga JT: The ‘dark side’ of chromatin remodelling: Repressive effects on transcription. Cell 1999;99:443–446.
- Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX, Harbour JW, Dean DC: Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. Cell 2000;101:79–89.
- Strobeck MW, Knudsen KE, Fribourg AF, DeCristofaro MF, Weissman BE, Imbalzano AN, Knudsen ES: BRG-1 is required for RB-mediated cell cycle arrest. Proc Natl Acad Sci USA 2000;97:7748–7753.
- Murphy DJ, Hardy SA, Engel DA: Human SWI-SNF component BRG1 represses transcription of the c-fos gene. Mol Cell Biol 1999;19:2724–2733.
- Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, Wang W, Kashanchi F, Shiekhattar R: BRCA1 is associated with a human SWI/SNF-related complex: Linking chromatin remodeling to breast cancer. Cell 2000;102:257–265.
- Wong AKC, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K, Ghaffari S, Iliev D, Penn B, Woodland A-M, Smith R, Salada G, Carillo A, Laity K, Gupte J, Swedlund B, Tavtigian SV, Teng DH-F, Lees E: BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines. Cancer Res 2000;60:6171–6177.
- Yanagihara K, Seyama T, Tsumuraya M, Kamada N, Yokoro K: Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the c-myc oncogene. Cancer Res 1991;51:381–386.
- Yokozaki H: Molecular characteristics of eight gastric cancer cell lines established in Japan. Pathol Int 2000;50:767–777.
- Ochiai A, Yasui W, Tahara E: Growth-promoting effect of gastrin on human gastric carcinoma cell line TMK-1. Jpn J Cancer Res 1985;76:1064–1071.
Japanese Research Society for Gastric Cancer: Japanese Classification of Gastric Carcinoma, ed 1 (English). Tokyo, Kanehara, 1995.
- Eads CA, Danenberg KD, Kawakami K, Saltz LB, Danenberg PV, Laird PW: CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression. Cancer Res 1999;59:2302–2306.
- Burns LG, Peterson CL: The yeast SWI-SNF complex facilitates binding of a transcriptional activator to nucleosomal sites in vivo. Mol Cell Biol 1997;17:4811–4819.
- Neely KE, Hassan AH, Wallberg AE, Steger DJ, Cairns BR, Wright APH, Workman JL: Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays. Mol Cell 1999;4:649–655.
- Sudarsanam P, Cao Y, Wu L, Laurent BC, Winston F: The nucleosome remodeling complex, Snf/Swi, is required for the maintenance of transcription in vivo and is partially redundant with the histone acetyltransferase, Gcn5. EMBO J 1999;18:3101–3106.
- Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA: Dissecting the regulatory circuitry of a eukaryotic genome. Cell 1998;95:717–728.
- Cheng SW, Davies KP, Yung E, Beltran RJ, Yu J, Kalpana GV: c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function. Nat Genet 1999;22:102–105.
- Ito T, Yamauchi M, Nishina M, Yamamichi N, Mizutani T, Ui M, Murakami M, Iba H: Identification of SWI/SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers. J Biol Chem 2001;276:2852–2857.
- Strobeck MW, DeCristofaro MF, Banine F, Weissman BE, Sherman LS, Knudsen ES: The BRG-1 subunit of the SWI/SNF complex regulates CD44 expression. J Biol Chem 2001;276:9273–9278.
- Ue T, Yokozaki H, Yamamoto S, Yasui W, Ishikawa T, Tahara E: Co-expression of osteopontin and CD44v9 in gastric cancer. Int J Cancer 1998;79:127–132.
- Yasui W, Kudo Y, Naka K, Fujimoto J, Ue T, Yokozaki H, Tahara E: Expression of CD44 containing variant exon 9 (CD44v9) in gastric adenomas and adenocarcinomas: Relation to the proliferation and progression. Int J Oncol 1998;12:1245–1251.
- Trouche D, LeChalony C, Mucjardt C, Yaniv M, Kouzarides T: RB and hbrm cooperate to repress the activation functions of E2F1. Proc Natl Acad Sci USA 1997;94:11268–11273.
- Wang W, Xue Y, Zhou S, Kuo A, Cairns BR, Crabtree GR: Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev 1996;10:2117–2130.
- Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O: Truncation mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 1998;394:203–206.
- Grand F, Kulkarni S, Chase A, Goldman KM, Gordon M, Cross NCP: Frequent deletion of hSNF5/INI1, a component of the SWI/SNF complex, in chronic myeloid leukemia. Cancer Res 1999;59:3870–3874.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.