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KMID : 0578319960060060719
Molecules and Cells
1996 Volume.6 No. 6 p.719 ~ p.725
Molecular Genetic Analysis of Tissue Inhibitors of metalloproteinase-1 Gene in Korean Colon Cancer Patients
Bae, Kwang-Ho
Kim, Min-Young/Kim, Eun-Hee
Abstract
Exons of Tissue inhibitors of metalloproteinase-1 (TIMP-1), a metastasis suppressor gene, were amplified by polymerase chain reaction, TIMP-1 alleles were classified, and nucleotide changes between tumor tissues and their normal counterparts were screened by SSCP in 11 Korean colon cancer patients. No mutational change between cancer tissues and their corresponding normal mucosas was observed. However, three distinct SSCP type alleles(named A, B, and C in this study) were detected in the exon spanning 56 carboxyl terminal amino acids and entire 3¢¥-UT. Subsequent sequence analysis revealed that the nucleotide sequence of the B type allele was the same as the published sequence [Carmichael, D. F.,Sommer) A., Thompson, R. C., Anderson, D. C., Smith, C. G., Welgus, H. G., and Stricklin, G. p. (1986) proc. Natl. Acad. Sci. USA 83, 2407-2411] but allele A showed a ¡°C¡± to ¡°T¡± transition in the 3¢¥-UT region. Allele C demonstrated a ¡°T¡± to ¡°C¡± transition in the third base of amino acid 158, resulting in no amino acid change. To our knowledge, this is the first dissection of TIMP-1 alleles at the nucleotide level. The relation between our typing and previous BglI RFLP allele typing [Aldred, M. A., and WrighL A. F. (1994) Mol. Cell. probes 8, 333-334] was studied. Type B was most abundantly feund (10 out of 15 ¡¿ chromosomes), type C allele was the second (4 out of 15X chromosomes) and type A was most rarely found (1 out of 15X chromosomes) among Korean colon cancer patients. Analysis of TIMP-1 alleles in healthy Koreans showed similar distribution pattern.
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