Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Induction of Metallothionein Gene by Laminin in Normal and Malignant Human Prostate Epithelial Cells

악성 단계별 인간 전립선 암세포에서 라미닌에 의한 metallothionein 유전자 발현유도 현상 연구

  • Ock, Mee-Sun (Department of Parasitology and Gnenetics, Kosin University College of Medicine) ;
  • Cha, Hee-Jae (Department of Parasitology and Gnenetics, Kosin University College of Medicine)
  • 옥미선 (고신대학교 의과대학 기생충학 유전학 교실) ;
  • 차희재 (고신대학교 의과대학 기생충학 유전학 교실)
  • Received : 2010.12.23
  • Accepted : 2010.12.30
  • Published : 2011.04.30
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Abstract

Metallothioneins (MT) are a group of low-molecular weight, cysteine-rich, intracellular proteins that are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins is associated with protection against DNA damage, oxidative stress, and apoptosis. Many studies have shown increased expression of MT in various human tumors, whereas MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. Using Northern blot analysis, we found that laminin induced expression of MT-1 in HSG and PC12 cells, which can be differentiated by laminin, but had no effect on MB-231, MDA-435, and PC-3 cells, which cannot be differentiated by laminin. In addition, we analyzed the expression level of the MT-1 gene in five prostate cancer cell lines possessing different metastatic potential. The expression of MT-1 in normal and less malignant cells (RWPE-1 and WPE1-NA22) was high and up-regulated by laminin, whereas the expression of MT-1 in WPE1-NB14, WPE1-NB11, and WPE1-NB26 cells (malignant) was extremely low and not elevated by laminin. These results suggest that the MT-1 gene is involved in laminin-mediated differentiation and affects the metastatic potential of tumor cells.

라미닌-1에 의해 분화가 유도되는 것으로 알려져 있는 HSG 및 PC-12에서는 라미닌-1에 의해 MT 유전자의 발현이 유도되었지만 반면 분화 역량을 지니지 않은 암세포인 유방암(MDA-231, MDA-435) 세포와 전립선 암인 PC-3 세포에서는 라미닌-1의 처리가 MT 유전자의 변화에 영향을 미치지 못하는 것이 관찰되었다. 라미닌-1에 의해 분화가 유도되는 현상 및 이에 따른 MT 유전자의 발현증가가 암의 전이 능력 및 악성화와 관계가 있는지를 관찰하기 위해 정상에서부터 전이 및 악성 정도가 다른 5가지 종류의 전립선 암을 대상으로 라미닌-1에 의한 MT 유전자의 발현 변화를 관찰한 결과 정상적인 전립선 외피세포인 RWPE-1과 전이 및 악성화가 낮은 WPE1-NA22의 경우 라미닌-1에 의해 MT 유전자의 발현이 증가하였으며, 악성화 정도가 높은 WPE1-NB14, WPE1-NB11, 및 WPE1-NB26에서는 라미닌-1의 처리에도 MT 유전자의 발현이 증가하지 않는 것이 관찰되었다. 이러한 결과를 통해 라미닌-1은 정상 세포의 분화를 유도하며 이에 따라 MT 유전자를 유도하며 분화가 유도되지 않는 악성 암에서는 MT 유전자의 발현이 유도되지 않는 것으로 확인되었다.

Keywords

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