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Title   한국인 간세포암에 있어서 p15INK4B / p16INK4A 및 Methylthioadenosine Phosphorylase 유전자의 이상 검색 ( Alterations of p15INK4B , p16INK4A and Methylthioadenosine Phosphorylase Gene in Korean Hepatocellular Carcinoma )
Publicationinfo   2000 Jan; 032(03): 553-563.
Key_word   Hepatocellular carcinoma , p16INK4A , Methylation , Methylthioadenosine phosphorylase
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Abstract   Purpose: We analyzed the gene status of p16INK4A, plSINK4B and MTAP (methylthio-adenosine phophorylase) in Korean hepatocellular carcinoma (HCC) to investigate whether the inactivation of these genes participated in hepatocarcinogenesis, and evaluated MTAP-targeted chemotherapy in MTAP-deficient cell lines. Material and Methods: We examined eleven primary HCC and 8 SNU cell lines using PCR, Southem blot analysis, PCR-SSCP, DNA sequencing, methylation-specific PCR, Western blot analysis, MTT assay, and crystal violet staining. Results: Mutations or deletion of the p16INK4A, 15INK4B, and MTAP genes were rare, but methylation of the p16INK4A promoter region was common in HCC. The base alterations of 3 untranslated region of p16INK4A exon 3 were also detected in 3 samples. In SNU cells, p16INK4A was not detectable, when treated with demethylating agent, high levels of re-expressed p161NK4A protein were detected. In MTAP-targeted chemotherapy experiment, methylthioadenosine (MTA) was able to rescue MTAP positive cell lines but not MTAP negative cell lines from growth inhibition by depletion of methionine and MTX treatment. Conclusion: These results suggest that de novo methylation of the p16INK4A promoter region seems to play an important role in the pathogenesis nf HCC. And treatment of MTX, combined with methionine depletion in the presence of MTA, may be a high selective treatment for MTAP negative HCC.
저 자   변호영(Ho Young Pyun),조재위(Jae We Cho),백원기(Won Ki Baik),박종욱(Jong Wook Park),박재복(Jae Pok Park),서민호(Min Ho Suh),서성일(Seong Il Suh)