Article: Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer
| Title | Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer |
|---|---|
| Authors | Li, 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 |
| Keywords | DTL/RAMP L2DTL Oncogene P21 P53 Tumourigenesis |
| Issue Date | 2009 |
| Publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc |
| Citation | British Journal Of Cancer, 2009, v. 101 n. 4, p. 691-698 [How to Cite?] DOI: http://dx.doi.org/10.1038/sj.bjc.6605202 |
| Abstract | Background: 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. |
| ISSN | 0007-0920 2011 Impact Factor: 5.042 2011 SCImago Journal Rankings: 0.561 |
| DOI | http://dx.doi.org/10.1038/sj.bjc.6605202 |
| ISI Accession Number ID | WOS:000268861000019 |
| PubMed Central ID | PMC2736823 |
| References | References in Scopus |
| dc.contributor.author | Li, J |
|---|---|
| dc.contributor.author | Ng, EKO |
| dc.contributor.author | Ng, YP |
| dc.contributor.author | Wong, CYP |
| dc.contributor.author | Yu, J |
| dc.contributor.author | Jin, H |
| dc.contributor.author | Cheng, VYY |
| dc.contributor.author | Go, MYY |
| dc.contributor.author | Cheung, PKF |
| dc.contributor.author | Ebert, MPA |
| dc.contributor.author | Tong, J |
| dc.contributor.author | To, KF |
| dc.contributor.author | Chan, FKL |
| dc.contributor.author | Sung, JJY |
| dc.contributor.author | Ip, NY |
| dc.contributor.author | Leung, WK |
| dc.date.accessioned | 2010-09-17T10:43:17Z |
| dc.date.available | 2010-09-17T10:43:17Z |
| dc.date.issued | 2009 |
| dc.description.abstract | Background: 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.nature | published_or_final_version |
| dc.identifier.citation | British 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.doi | http://dx.doi.org/10.1038/sj.bjc.6605202 |
| dc.identifier.epage | 698 |
| dc.identifier.hkuros | 168713 |
| dc.identifier.isi | WOS:000268861000019 |
| dc.identifier.issn | 0007-0920 2011 Impact Factor: 5.042 2011 SCImago Journal Rankings: 0.561 |
| dc.identifier.issue | 4 |
| dc.identifier.openurl | ![]() |
| dc.identifier.pmcid | PMC2736823 |
| dc.identifier.pmid | 19672268 |
| dc.identifier.scopus | eid_2-s2.0-68749109533 |
| dc.identifier.spage | 691 |
| dc.identifier.uri | http://hdl.handle.net/10722/92344 |
| dc.identifier.volume | 101 |
| dc.language | eng |
| dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc |
| dc.publisher.place | United Kingdom |
| dc.relation.ispartof | British Journal of Cancer |
| dc.relation.references | References in Scopus |
| dc.subject.mesh | Apoptosis - physiology |
| dc.subject.mesh | Immunohistochemistry |
| dc.subject.mesh | Nuclear Proteins - genetics - metabolism |
| dc.subject.mesh | Stomach Neoplasms - genetics - metabolism |
| dc.subject.mesh | Tumor Markers, Biological - analysis |
| dc.subject | DTL/RAMP |
| dc.subject | L2DTL |
| dc.subject | Oncogene |
| dc.subject | P21 |
| dc.subject | P53 |
| dc.subject | Tumourigenesis |
| dc.title | Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer |
| dc.type | Article |
Author Affiliations
- Prince of Wales Hospital Hong Kong
- Hong Kong University of Science and Technology
- Chinese University of Hong Kong
- Technische Universität München


