Article: Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer

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TitleIdentification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer
AuthorsLi, J3
Ng, EKO3
Ng, YP2
Wong, CYP3
Yu, J3
Jin, H3
Cheng, VYY4
Go, MYY3
Cheung, PKF3
Ebert, MPA2
Tong, J3
To, KF3
Chan, FKL3
Sung, JJY3
Ip, NY2
Leung, WK1 3
KeywordsDTL/RAMP
L2DTL
Oncogene
P21
P53
Tumourigenesis
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc
CitationBritish Journal Of Cancer, 2009, v. 101 n. 4, p. 691-698 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.bjc.6605202
AbstractBackground: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis.Methods: RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro.Results: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P0.01) and soft agar colony formation (P0.001), but induced apoptosis and G 2 /M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar.Conclusion: Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy. © 2009 Cancer Research UK.
ISSN0007-0920
2011 Impact Factor: 5.042
2011 SCImago Journal Rankings: 0.561
DOIhttp://dx.doi.org/10.1038/sj.bjc.6605202
ISI Accession Number IDWOS:000268861000019
PubMed Central IDPMC2736823
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLi, J
dc.contributor.authorNg, EKO
dc.contributor.authorNg, YP
dc.contributor.authorWong, CYP
dc.contributor.authorYu, J
dc.contributor.authorJin, H
dc.contributor.authorCheng, VYY
dc.contributor.authorGo, MYY
dc.contributor.authorCheung, PKF
dc.contributor.authorEbert, MPA
dc.contributor.authorTong, J
dc.contributor.authorTo, KF
dc.contributor.authorChan, FKL
dc.contributor.authorSung, JJY
dc.contributor.authorIp, NY
dc.contributor.authorLeung, WK
dc.date.accessioned2010-09-17T10:43:17Z
dc.date.available2010-09-17T10:43:17Z
dc.date.issued2009
dc.description.abstractBackground: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis.Methods: RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro.Results: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P0.01) and soft agar colony formation (P0.001), but induced apoptosis and G 2 /M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar.Conclusion: Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy. © 2009 Cancer Research UK.
dc.description.naturepublished_or_final_version
dc.identifier.citationBritish Journal Of Cancer, 2009, v. 101 n. 4, p. 691-698 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.bjc.6605202
dc.identifier.doihttp://dx.doi.org/10.1038/sj.bjc.6605202
dc.identifier.epage698
dc.identifier.hkuros168713
dc.identifier.isiWOS:000268861000019
dc.identifier.issn0007-0920
2011 Impact Factor: 5.042
2011 SCImago Journal Rankings: 0.561
dc.identifier.issue4
dc.identifier.openurl
dc.identifier.pmcidPMC2736823
dc.identifier.pmid19672268
dc.identifier.scopuseid_2-s2.0-68749109533
dc.identifier.spage691
dc.identifier.urihttp://hdl.handle.net/10722/92344
dc.identifier.volume101
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc
dc.publisher.placeUnited Kingdom
dc.relation.ispartofBritish Journal of Cancer
dc.relation.referencesReferences in Scopus
dc.subject.meshApoptosis - physiology
dc.subject.meshImmunohistochemistry
dc.subject.meshNuclear Proteins - genetics - metabolism
dc.subject.meshStomach Neoplasms - genetics - metabolism
dc.subject.meshTumor Markers, Biological - analysis
dc.subjectDTL/RAMP
dc.subjectL2DTL
dc.subjectOncogene
dc.subjectP21
dc.subjectP53
dc.subjectTumourigenesis
dc.titleIdentification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer
dc.typeArticle
Author Affiliations
  1. Prince of Wales Hospital Hong Kong
  2. Hong Kong University of Science and Technology
  3. Chinese University of Hong Kong
  4. Technische Universität München