Farnesylcysteine Methyltransferase Activity and Ras Protein Expression in Human Stomach Tumor Tissue

  • Han, Eui-Sik (Department of Pharmacy, National Instiute of Toxicological Research, Korea Food and Drug Administration) ;
  • Oh, Hye-Young (Department of Toxicology, National Instiute of Toxicological Research, Korea Food and Drug Administration) ;
  • Ha, Kwang-Won (Department of Toxicology, National Instiute of Toxicological Research, Korea Food and Drug Administration) ;
  • Han, Beom-Seok (Department of Pathology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Hong, Seok-Min (Department of Pathology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Han, Jung-Whwan (Department of Pharmacy, National Instiute of Toxicological Research, Korea Food and Drug Administration) ;
  • Hong, Sung-Youl (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Noh, Sung-Hun (Department of Surgery, Yonse University College of Medinine) ;
  • Lee, Hyang-Woo (Department of Pharmacy, National Instiute of Toxicological Research, Korea Food and Drug Administration)
  • Published : 1998.08.01

Abstract

The processing pathway of G-proteins and Ras family proteins includes the isoprenylation of the cysteine residue, followed by proteolysis of three terminal residues and .alpha.-carboxyl methyl esterification of the cysteine residue. Farnesylcysteine methyltransferase (FCMT) activity is responsible for the methylation reaction which play a role in the membrane attachment of a variety of cellular proteins. Four kinds of Ras protein (c-Ha-ras, c-N-Ras, c-Ki-Ras, pan-Ras) expression were detected in adenocarcinoma of human tissue by immunohistochemical method, and hematoxylin and eosin staining. The level of Ras protein in human stomach tumor tissues was much higher than in normal and peritumoral regions of the same biopsy samples. The FCMT activities of each cellular fractions were high in mitochondrial fraction followed by microsomal fraction, whole homogenate and cytosolic fraction. The inhibitory effect on FCMT activity on stomach tumor tissue was determined after treatment with 0.25 $\mu\textrm{M}$ of S-adenosyl-$_L$-homocysteine. S-adenosyl-$_L$-homocysteine inhibited FCMT activity from 11.2% to 30.5%. These results suggested that FCMT might be involved in Ras proteins activity.

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