File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Frequent Inactivation of Axon Guidance Molecule RGMA in Human Colon Cancer Through Genetic and Epigenetic Mechanisms

TitleFrequent Inactivation of Axon Guidance Molecule RGMA in Human Colon Cancer Through Genetic and Epigenetic Mechanisms
Authors
Issue Date2009
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2009, v. 137 n. 1, p. 176-187 How to Cite?
AbstractBackground & Aims: Repulsive guidance molecule member A (RGMA) is a glycosylphosphatidylinositol-anchored glycoprotein and axon guidance molecule that signals through its receptor, neogenin (NEO1), a homologue of the deleted-in-colorectal cancer (DCC) gene. RGMA also functions as a bone morphogenetic protein (BMP) coreceptor. We studied the potential roles of RGMA and NEO1 in colorectal cancer (CRC) pathogenesis. Methods: We analyzed expression of RGMA and NEO1, as well as their epigenetic and genetic changes, in a large series of CRC samples, normal colon tissues, adenomas, and cell lines. These studies were accompanied by in vitro functional assay. Results: RGMA and NEO1 expression were significantly down-regulated in most CRCs, adenomas, and cell lines. RGMA was frequently silenced by promoter methylation in CRCs (86.7%), adenomas (90.9%), and CRC cell lines (92.3%) but not in normal colon tissues; allelic imbalance of RGMA and NEO1 was observed in 40% and 49% of CRCs, respectively. In CRC samples, reduced RGMA levels were significantly associated with mismatch repair deficiency or mutations in KRAS or BRAF. Exposure to 5-aza-2′-deoxycytidine restored RGMA expression in CRC cell lines. Transfection of RGMA into CRC cells suppressed cell proliferation, migration, and invasion and also increased apoptosis in response to DNA-damaging agent. Conclusions: The frequent genetic and epigenetic inactivation of RGMA in CRCs and adenomas along with its in vitro function collectively support its role as a tumor suppressor in colon cells. These findings add to the expanding list of axon guidance molecules with disrupted function during colon carcinogenesis and create new opportunities for early detection and drug development. © 2009 AGA Institute.
Persistent Identifierhttp://hdl.handle.net/10722/88334
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170
ISI Accession Number ID
Funding AgencyGrant Number
Council of the Hong Kong Special Administrative RegionHKU7622/05M
HKU7697/08M
Funding Information:

This work is supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region (Project No. HKU7622/05M and HKU7697/08M).

References

 

DC FieldValueLanguage
dc.contributor.authorLi, VSWen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorChan, TLen_HK
dc.contributor.authorYan, HHNen_HK
dc.contributor.authorLaw, WLen_HK
dc.contributor.authorYeung, BHYen_HK
dc.contributor.authorChan, ASYen_HK
dc.contributor.authorTsui, WYen_HK
dc.contributor.authorSo, Sen_HK
dc.contributor.authorChen, Xen_HK
dc.contributor.authorLeung, SYen_HK
dc.date.accessioned2010-09-06T09:42:01Z-
dc.date.available2010-09-06T09:42:01Z-
dc.date.issued2009en_HK
dc.identifier.citationGastroenterology, 2009, v. 137 n. 1, p. 176-187en_HK
dc.identifier.issn0016-5085en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88334-
dc.description.abstractBackground & Aims: Repulsive guidance molecule member A (RGMA) is a glycosylphosphatidylinositol-anchored glycoprotein and axon guidance molecule that signals through its receptor, neogenin (NEO1), a homologue of the deleted-in-colorectal cancer (DCC) gene. RGMA also functions as a bone morphogenetic protein (BMP) coreceptor. We studied the potential roles of RGMA and NEO1 in colorectal cancer (CRC) pathogenesis. Methods: We analyzed expression of RGMA and NEO1, as well as their epigenetic and genetic changes, in a large series of CRC samples, normal colon tissues, adenomas, and cell lines. These studies were accompanied by in vitro functional assay. Results: RGMA and NEO1 expression were significantly down-regulated in most CRCs, adenomas, and cell lines. RGMA was frequently silenced by promoter methylation in CRCs (86.7%), adenomas (90.9%), and CRC cell lines (92.3%) but not in normal colon tissues; allelic imbalance of RGMA and NEO1 was observed in 40% and 49% of CRCs, respectively. In CRC samples, reduced RGMA levels were significantly associated with mismatch repair deficiency or mutations in KRAS or BRAF. Exposure to 5-aza-2′-deoxycytidine restored RGMA expression in CRC cell lines. Transfection of RGMA into CRC cells suppressed cell proliferation, migration, and invasion and also increased apoptosis in response to DNA-damaging agent. Conclusions: The frequent genetic and epigenetic inactivation of RGMA in CRCs and adenomas along with its in vitro function collectively support its role as a tumor suppressor in colon cells. These findings add to the expanding list of axon guidance molecules with disrupted function during colon carcinogenesis and create new opportunities for early detection and drug development. © 2009 AGA Institute.en_HK
dc.languageengen_HK
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastroen_HK
dc.relation.ispartofGastroenterologyen_HK
dc.subject.meshAdenoma - genetics - metabolism - pathologyen_HK
dc.subject.meshAllelic Imbalanceen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCell Movement - geneticsen_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshColonic Neoplasms - genetics - metabolism - pathologyen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshDNA Mismatch Repair - geneticsen_HK
dc.subject.meshGPI-Linked Proteinsen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshGene Silencingen_HK
dc.subject.meshGenes, Tumor Suppressoren_HK
dc.subject.meshHumansen_HK
dc.subject.meshMembrane Proteins - genetics - metabolismen_HK
dc.subject.meshMutationen_HK
dc.subject.meshNeoplasm Invasivenessen_HK
dc.subject.meshNerve Tissue Proteins - genetics - metabolismen_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshProto-Oncogene Proteins - geneticsen_HK
dc.subject.meshProto-Oncogene Proteins B-raf - geneticsen_HK
dc.subject.meshTransfectionen_HK
dc.subject.meshras Proteins - geneticsen_HK
dc.titleFrequent Inactivation of Axon Guidance Molecule RGMA in Human Colon Cancer Through Genetic and Epigenetic Mechanismsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0016-5085&volume=137&issue=1&spage=176&epage=87&date=2009&atitle=Frequent+inactivation+of+axon+guidance+molecule+RGMA+in+human+colon+cancer+through+genetic+and+epigenetic+mechanismsen_HK
dc.identifier.emailChan, TL: tlchan@hku.hken_HK
dc.identifier.emailLaw, WL: lawwl@hkucc.hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hkucc.hku.hken_HK
dc.identifier.authorityChan, TL=rp00418en_HK
dc.identifier.authorityLaw, WL=rp00436en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/j.gastro.2009.03.005en_HK
dc.identifier.pmid19303019-
dc.identifier.scopuseid_2-s2.0-67649215234en_HK
dc.identifier.hkuros158768en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67649215234&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume137en_HK
dc.identifier.issue1en_HK
dc.identifier.spage176en_HK
dc.identifier.epage187en_HK
dc.identifier.eissn1528-0012-
dc.identifier.isiWOS:000267410100028-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, VSW=55055323800en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridChan, TL=7402687537en_HK
dc.identifier.scopusauthoridYan, HHN=36984690100en_HK
dc.identifier.scopusauthoridLaw, WL=7103147867en_HK
dc.identifier.scopusauthoridYeung, BHY=24402173100en_HK
dc.identifier.scopusauthoridChan, ASY=7403168075en_HK
dc.identifier.scopusauthoridTsui, WY=7005623159en_HK
dc.identifier.scopusauthoridSo, S=7102397384en_HK
dc.identifier.scopusauthoridChen, X=8978110800en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats