Differential Expression of N-Acetylglucosaminyltransferase-3 and-V Activities in Human Hepatoma Cells and Colon Cancer Cells : Implication of Cancer Specific-Glycoantigen Synthesis in Malignant Transformation 악성화과정중 암특이당쇄항원의 의미와 억제 = 사람 간암 및 대장암세포에서 암당쇄항원합성효소 N-acetylglucosaminyltransferase-3 과 V 활성의 특이적 발현

국문 초록 (Abstract)

본 연구그룹은 정상세포가 형질전환되어가는 과정에서 당쇄항원생합성을 하는 효소가 N-아세틸글루코사민전이효소임을 밝히고 이들의 분자세포생물학적인 연구와 Transgenic mouse 개발을 통한 암예방,치료,조기진단에 대한 연구를 수행하여 왔다. 본 논문에서는 사람 간암 및 대장암세포에서 암당쇄항원합성효소 N-acetylglucosaminyltransferase (GlcNAc-transferase)- Ⅲ 과 V활성의 발현정도를 정상세포들과 비교하였다. 정상세포들의 활성은 매우 낮았으며, 간암세포에서 GlcNAc-transferase-Ⅲ활성이GlcNAc-transferase-V보다 높았으나, 대장암세포에서는 훨씬 낮게 발현되었다. 기질로서 GlcN,GlcN-biant-PA와 UDP-GlcNAc를 사용하였을 때, 각각의 효소들은 간암과 대장암세포에서 이들의 암전이능력에 의존하여 각각 다른 반응특성을 나타내었다. 이러한 결과들은 GlcNAc-transferase-Ⅲ 와 V유전자발현(mRNA)을 위한 RT-PCR결과에서도 동일하였다. 이러한 암세포에서 암당쇄항원의 생합성에 관여하는 N-acetylglucosamine 전이효소의 특이적인 발현과 악성화과정중 암특이당쇄항원과의 관계를 분자세포생물학적 및 기능성식품학적인 측면에서 토론하였다.

다국어 초록 (Multilingual Abstract)

UDP-N-Aacetylglucosamine:α-6-D-mannoside β-1,6N-acetylglucosaminyltransferase-Ⅲ (GlcNAc-transferase-Ⅲ) and UDP-N-Aacetylglucosamine : α-6-D-mannoside β-1,6N-acetylglucosaminyltransferase - V (GlcNAc -transferase - V )activities were determined in human hepatoma cell lines of Hep3B and HepG2, and also compared with those of normal liver tissues and primary hepatocytes. GlcNAc-transferase-Ⅲ activities were higher than those of GlcNAc-transferase-V in hepatic carcinomca cells. In contrast, the two enzyme activities were assayed in highly metastatic colon cancer cells, GlcNAc-transferase-V activities were much higher than those of GlcNAc-transferase-Ⅲ . When GlcN,GlcN-biant-PA and UDP-GlcNAc were used as substrates, the enzymes displayed different kinetic properties between hepatic and colon cancer cells, depending on their metastatic potentials. Normal cells of two origins are characterized by a very low level of GlcNAc-transferase- Ⅲ and -V activities, whereas hepatoma and colon cancer cells cotained high activities. These data were supported by reverse transcription-polymerase chain reaction results, showing that expression of the GlcNAc-transferase-Ⅲ and V mRNAs increased in proportion to the enzymatic activities. Although the mechanism underlying the induction of this enzymes is unknown, lectin blot analysis showed that oligosaccharides in many glycopnteins were observed in cancer cells. Thus, this is the first demonstration of GlcNAc-transferase-Ⅲ and V activities in human hepatoma and colon cell lines. Molecular aspects of two GlcNAc-transferases in tumorigenesis and metastasis will be extensively discussed.