非小细胞肺癌中P53表达的不同亚细胞定位及功能意义的研究

目的:探讨非小细胞肺癌(NSCLC)中不同亚细胞定位P53蛋白及其可能的功能意义。方法:以免疫组化及流式细胞分析术研究了43例NSCLC病人肿瘤组织P53表达定位与G₁/S检查点功能及DNA含量的关系。结果:发现P53蛋白不同的亚细胞定位与病人的病程密切相关,同时,在P53核表达定位的病人肿瘤组织细胞S期比例明显增多而G₀－G₁期比例明显较胞浆表达病人减少,G₂－M期比例及DNA指数在两组间无明显差异。结论:不同亚细胞定 位的P53蛋白具有不同的G₁/S检查点调节功能,胞浆P53蛋白仍有部分G₁/S检查点调控功能,因此出现较少的SPF及较多的G₀－G₁细胞,代表了恶性度较低的细胞亚群;而核表达阳性P53蛋白具有更差的G₁/S检查点调控功能,代表了恶性度较高的肿瘤亚群,这与肿瘤进展可能有关。

P53 overexpression in different subcellular location in non small cell lung cancer

AIM: Nuclear P53 localization was considered to be proof of mutation, cytoplasmic staining has also been signalled. In this study, special attention has paid to protein subcelluler localization. A different functional meaning may attributed to tumor biological characteristic and evolution. METHODS: Immunohistochemical approach and flow cytometry were used to explored the relationship between P53 overexpression pattern (nuclear and cytoplas- mic) and G₁/S checkpoint function of P53 protein in cell cycle. RESULTS: Two patterns of P53 overexpression are related to disease stage significantly. S - phase fraction (SPF) was higher and G₀-G₁ phase fraction was lower in P53 nuclear pattern than cytoplasmic (SPF, 42.42± 5.45/14. 12± 442, G₀-G₁: 53.04 ± 6.14／75.56 ± 4.46, respectively P < 0.05). No difference was found in G₂ - M phase fraction and DNA index between two patterns. CONCLUSION: Most of the cells showing cytoplasmic P53 overexpression pattern are properly arrested in G/S checking point, which may represent an early tumor cell population with low grade of neoplastic development. In contrast, inactivated product detectable at nuclear level possible carry a mutated P53 associated with tumor progression. The mechanism of P53 cytoplasmic location is not clear.