Exogenous wild-type p16INK4A gene induces delayed cell proliferation and promotes chemosensitivity through decreased pRB and increased E2F-1 expressions.
Exogenous wild-type p16INK4A gene induces delayed cell proliferation and promotes chemosensitivity through decreased pRB and increased E2F-1 expressions.
复制标题
外源野生型 p16INK4A 基因通过减少 pRB 和增加 E2F-1 表达来诱导细胞增殖延迟并提高化疗敏感性。
DOI：
10.3892/ijmm.12.1.61
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发表时间：
2003
影响因子：
5.4
通讯作者：
Jae‐We Cho
中科院分区：
文献类型：
--
作者：
Y. Jeong;Ki;Jae;Jong;W. Baek;S. Suh;M. Suh;Je;Jae‐We Cho
人胃癌SNU 484细胞表达突变型p16，其迁移速度慢于野生型p16。我们构建了含人p16基因的表达载体，以评价外源p16基因表达对SNU 484细胞增殖的影响，探讨p16基因在肿瘤基因治疗中的潜在应用。稳定表达野生型p16的细胞，通过下调CDK4依赖的激酶活性，其生长速度比模拟细胞和未感染细胞慢2倍。当瞬时将模拟或p16编码载体导入细胞时，模拟细胞显示出比野生型p16更大的存活集落。此外，p16表达稳定的转染体在化疗药物作用下易发生细胞死亡，且呈剂量依赖关系。根据Western印迹分析，pRb的表达减少和E2F-1的表达增加都可能与细胞死亡的易感性有关。我们的数据表明，外源野生型p16诱导胃癌细胞系延迟细胞增殖并提高对化疗的敏感性，这意味着p16在癌症基因治疗中的前景。
Human gastric cancer SNU 484 cells express mutant p16, which migrates slower than the wild-type p16. We constructed an expression vector containing human p16 cDNA to evaluate the cytotoxic effects of exogenous p16 expression on SNU 484 cell proliferation and to explore the potential use of p16 in cancer gene therapy. The stable transfectant expressing wild-type p16, showed a 2-fold slower growth rate than mock and non-infected cells through down-regulation of CDK4-dependent kinase activity. When cells were transiently transfected with mock or p16 encoded vector, the mock cells showed larger survival colonies than those of wild-type p16. Furthermore, p16-expressing stable transfectant was readily progressed into cell death by combination with treatment of chemotherapeutic drug in a dose-dependent manner. According to western blot analysis, both decreased expression of pRB and increased expression of E2F-1 may contribute to the susceptibility of cell death. Our data indicate that exogenous wild-type p16 induces delayed cell proliferation and promotes chemo-sensitivity in the gastric cancer cell line, implying the promise of p16 in cancer gene therapy.