Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-5-4
pubmed:abstractText
The aim of this study was to assess whether combined evaluation of O6-methylguanine methyltransferase (MGMT) and hMLH1 status determines sensitivity to monofuntional alkylating agents such as N-methyl-N-nitrosourea (MNU) and dacarbazine (DTIC) against gallbladder carcinoma cells. The molecular mechanism behind MGMT and hMLH1 status affecting the cell cycle was also addressed. Using 5 gallbladder cancer carcinoma lines and 1 colon carcinoma cell line (SW48), MGMT and hMLH1 expression was analyzed using RT-PCR and Western blotting. MGMT and hMLH1 status in the 6 cell lines was compared with drug sensitivity to MNU. As a result, cell lines that were MGMT-/hMLH1+ had the highest sensitivity to MNU, compared with MGMT+/hMLH1+ and MGMT-/hMLH1- cells. In flow cytometric analysis, G2-M cell cycle arrest was specifically observed in GB-d1 cells with MGMT-/hMLH1+ and expression of cyclin A and Cdc2 in GB-d1 cells was significantly reduced by MNU treatment, but not observed in KMG-C cells with MGMT+/hMLH1+. Finally, we assessed the in vitro and in vivo effect of the clinically used alkylating agent DTIC in these cells. The highest sensitivity to DTIC was also observed in MGMT-/hMLH1+. In conclusion, MNU suppressed cell proliferation of MGMT-/hMLH1+ gallbladder carcinoma cells by arresting the cell cycle at the G2-M phase, accompanied by down-regulation of cyclin A and Cdc2. These results indicated that expression of MGMT and hMLH1 could be used to select candidates for alkylating agent chemotherapy against gallbladder carcinoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Alkylating, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Dacarbazine, http://linkedlifedata.com/resource/pubmed/chemical/MLH1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Methylnitrosourea, http://linkedlifedata.com/resource/pubmed/chemical/Mlh1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/O(6)-Methylguanine-DNA..., http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1653-61
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15870882-Adaptor Proteins, Signal Transducing, pubmed-meshheading:15870882-Animals, pubmed-meshheading:15870882-Antineoplastic Agents, Alkylating, pubmed-meshheading:15870882-Carrier Proteins, pubmed-meshheading:15870882-Cell Division, pubmed-meshheading:15870882-Cell Line, Tumor, pubmed-meshheading:15870882-Dacarbazine, pubmed-meshheading:15870882-Female, pubmed-meshheading:15870882-Flow Cytometry, pubmed-meshheading:15870882-G2 Phase, pubmed-meshheading:15870882-Gallbladder Neoplasms, pubmed-meshheading:15870882-Humans, pubmed-meshheading:15870882-Methylnitrosourea, pubmed-meshheading:15870882-Mice, pubmed-meshheading:15870882-Mice, Inbred BALB C, pubmed-meshheading:15870882-Neoplasm Proteins, pubmed-meshheading:15870882-Neoplasms, Experimental, pubmed-meshheading:15870882-Nuclear Proteins, pubmed-meshheading:15870882-O(6)-Methylguanine-DNA Methyltransferase, pubmed-meshheading:15870882-RNA, Messenger
pubmed:year
2005
pubmed:articleTitle
Deficient MGMT and proficient hMLH1 expression renders gallbladder carcinoma cells sensitive to alkylating agents through G2-M cell cycle arrest.
pubmed:affiliation
Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan.
pubmed:publicationType
Journal Article