Mitotic checkpoint protein hsMAD2 as a marker predicting liver metastasis of human gastric cancers

Citation
K. Tanaka et al., Mitotic checkpoint protein hsMAD2 as a marker predicting liver metastasis of human gastric cancers, JPN J CANC, 92(9), 2001, pp. 952-958
Citations number
17
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
JAPANESE JOURNAL OF CANCER RESEARCH
ISSN journal
0910-5050 → ACNP
Volume
92
Issue
9
Year of publication
2001
Pages
952 - 958
Database
ISI
SICI code
0910-5050(200109)92:9<952:MCPHAA>2.0.ZU;2-X
Abstract
hsMAD2, the human homologue of mitotic arrest deficient 2 (MAD2), is a key component of the mitotic checkpoint system. Recently, mutations and decreas ed expression of mitotic checkpoint genes including hsMAD2 have been report ed in cancer cell lines with defective mitotic checkpoint. However, the gen etic alterations in the genomic hsMAD2 gene have not been determined in gas tric cancers. Moreover. the biological implications of the overexpressed hs MAD2 in primary cancers are unknown. In this study, we analyzed 32 primary gastric cancers with polymerase chain reaction (PCR) amplification of all e xons, including flanking intronic sequences, of the genomic hsMAD2 gene fol lowed by direct DNA sequencing. We also measured the hsMAD2 protein levels in cancer and normal tissues by semi-quantitative immunoblotting. No mutati ons were found in the coding sequences, although three single nucleotide po lymorphisms (SNPs) were identified in the noncoding sequences in 13 of 32 p atients. These SNPs were not associated with either hsMAD2 expression or di sease progression. The semi-quantitative western blot analysis showed hsMAD 2 was significantly overexpressed in gastric cancer tissues compared with c orresponding normal tissues (P<0.001). The calculated ratio of the hsMAD2 p rotein in cancer tissue (C) to that in corresponding normal tissue (N) (C/N ratio) was significantly higher in patients with well differentiated adeno carcinoma (P=0.0274) or with synchronous liver metastasis (P=0.0025). A C/N ratio greater than 3 was observed more frequently in patients with synchro nous liver metastasis. Therefore, C/N ratio >3 may be clinically important as a predictive indicator for metachronous liver metastasis of gastric canc ers.