Isolation of Two Novel Genes, Down‐regulated in Gastric Cancer (original) (raw)

Abstract

Using a differential display technique, we identified two genes that are down‐regulated in human gastric cancer tissue as compared to normal gastric mucosa. The down‐regulated expression of these genes in gastric cancer tissue was confirmed by northern blotting analysis and RT‐PCR. One, CA11, was a novel gene expressed predominantly in the stomach and was depleted in all of the gastric cancer cell lines examined. The other gene, GC36, was homologous to the digestive tract‐specific calpain gene, nCL‐4. The expression of both GC36 and nCL‐4 was suppressed or depleted in gastric cancer cell lines of differentiated and poorly differentiated types. This is the first report of genes, the expression of which is down‐regulated with considerable frequency in gastric cancer.

Keywords: Differential display, Down‐regulated expression, Gastric cancer, Digestive tractspecific calpain nCL‐4

Full Text

The Full Text of this article is available as a PDF (173.0 KB).

REFERENCES

• 1.) Tsugawa , K. , Yonemura , Y. , Hirono , Y. , Fushida , S. , Kaji , M. , Miwa , K. , Miyazaki , I. and Yamamoto , H.Amplification of the c‐met, c‐erbB‐2 and epidermal growth factor receptor gene in human gastric cancers: correlation to clinical features . Oncology , 55 , 475 – 481 ( 1998. ). [DOI] [PubMed] [Google Scholar]
• 2.) Tahara , E.Genetic alterations in human gastrointestinal cancers . Cancer , 75 ( Suppl. ), 1410 – 1417 ( 1995. ). [DOI] [PubMed] [Google Scholar]
• 3.) Guilford , P. , Hopkins , J. , Harraway , J. , McLeod , M. , McLeod , N. , Harawira , P. , Taite , H. , Scoular , R. , Miller , A. and Reeve , A. E.E‐cadherin germline mutations in familial gastric cancer . Nature , 392 , 402 – 405 ( 1998. ). [DOI] [PubMed] [Google Scholar]
• 4.) Liang , P. and Pardee , A. B.Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction . Science , 257 , 967 – 971 ( 1992. ). [DOI] [PubMed] [Google Scholar]
• 5.) Yoshikawa , Y. , Mukai , H. , Asada , K. , Hino , F. and Kato , I.Differential display with carboxy‐X‐rhodamine‐labeled primers and the selection of differentially amplified cDNA fragments without cloning . Anal. Biochem. , 256 , 82 – 91 ( 1998. ). [DOI] [PubMed] [Google Scholar]
• 6.) Wawer , C. , Rüggeberg , H. , Meyer , G. and Muyzer , G.A simple and rapid electrophoresis method to detect sequence variation in PCR‐amplified DNA fragments . Nucleic Acids Res. , 23 , 4928 – 4929 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
• 7.) Lee , H.‐J. , Sorimachi , H. , Jeong , S.‐Y. , Ishiura , S. and Suzuki , K.Molecular cloning and characterization of a novel tissue‐specific calpain predominantly expressed in the digestive tract . Biol. Chem. , 379 , 175 – 183 ( 1998. ). [DOI] [PubMed] [Google Scholar]
• 8.) Croall , D. E. and DeMartino , G. N.Calcium‐activated neutral protease (calpain) system; structure, function, and regulation . Physiol. Rev. , 71 , 813 – 847 ( 1991. ). [DOI] [PubMed] [Google Scholar]
• 9.) Sorimachi , H. , Ishiura , S. and Suzuki , K.A novel tissuespecific calpain species expressed predominantly in the stomach comprises two alternative splicing products with and without Ca2+‐binding domain . J. Biol. Chem. , 268 , 19476 – 19482 ( 1993. ). [PubMed] [Google Scholar]
• 10.) Lee , H.‐J. , Tomioka , S. , Kinbara , K. , Masumoto , H. , Jeong , S.‐Y. , Sorimachi , H. , Ishiura , S. and Suzuki , K.Characterization of a human digestive tract‐specific calpain, nCL‐4, expressed in the baculovirus system . Arch. Biochem. Biophys. , 362 , 22 – 31 ( 1999. ). [DOI] [PubMed] [Google Scholar]
• 11.) Braun , C. , Engel , M. , Seifert , M. , Theisinger , B. , Seitz , G. , Zang , K. D. and Welter , C.Expression of calpain I messenger RNA in human renal cell carcinoma: correlation with lymph node metastasis and histological type . Int. J. Cancer , 84 , 6 – 9 ( 1999. ). [DOI] [PubMed] [Google Scholar]