外源性p16基因表达可抑制人胃癌细胞的恶性增殖

Exogenous mtsl/p16 gene suppresses tumorigenicity of human gastric cancer cell line.

目的探讨ｍｔｓｌ／ｐ１６基因在肿瘤发生发展过程中的作用及在临床基因诊断和基因治疗中的应用前景。方法构建ｍｔｓｌ／ｐ１６基因的表达载体并导入表达水平下调的ＰＡＭＣ８２细胞，用ＰＣＲ、Ｎｏｒｔｈｅｒｎ杂交、ｍＲＮＡ原位杂交和Ｗｅｓｔｅｒｎ杂交对获得Ｇ４１８抗性的细胞进行外源性ｍｔｓｌ／ｐ１６基因整合及表达的鉴定。对导入外源性ｐ１６基因的细胞进行裸鼠致瘤能力及病理学特性分析。结果转染ｐ１６基因的ＰＡＭＣ８２细胞（命名为ＰＡＭＣｐ１６）有外源性ｍｔｓｌ／ｐ１６基因的整合及表达，在裸鼠中的致瘤性显著降低。肿瘤组织病理分析结果显示，ＰＡＭＣｐ１６细胞形成的肿瘤，其分化程度优于ＰＡＭＣ８２细胞。结论导入外源性ｍｔｓｌ／ｐ１６基因可抑制肿瘤细胞的恶性增殖和促进细胞分化。

Objective To determine the effect on cell growth and tumorigenicity of mtsl/p16 gene in human gastric cancer cell line. Methods mtsl/p16 gene vector was constructed and transfected into PAMC82 cells which retains down regulated mtsl/p16 gene expression. Integration and expression of exogenous mtsl/p16 gene were confirmed by PCR, Northern blot, mRNA in situ hybridization and Western blot techniques. Cell morphology was observed in regular culture medium and tumorigenicity in nude mice.Results The growth of the cells transferred with mtsl/p16 gene (named as PAMCp16) was dramatically inhibited in nude mice as compared to that of the parental PAMC82 cells. Histologically, the tumor grown from PAMCp16 cells was much better differentiated than that from the parental ones. Conclusion Tumorigenicity of a human gastric cancer cell line in nude mice can be inhibited by transduced exogenous mtsl/p16 gene. mtsl/p16 gene may have potential value in gene diagnosis and gene therapy.