恶性黑色素瘤细胞凋亡特点的研究进展

The characteristics of invasion and metastasis in malignant melanoma and apoptosis

对外界广泛刺激原的反应失去诱导细胞凋亡的能力,使恶性黑色素瘤在进展和转移方面获得选择的优势及对常规治疗方法的不敏感性。基因组的突变(p53)、G蛋白和蛋白激酶(Ras等)转录、转录后水平及转录因子效应基因(NF-κB、c-jun、stat3、ATF2)的变化、抗凋亡基因(Bcl-2、Bcl-XL、surviving、ML-IAP等)的表达上调,均影响TNF、Fas、TRAIL受体等诱导细胞凋亡的途径,在恶性黑色素瘤获得抗凋亡能力方面起重要作用。参与凋亡通路信号传导的分子蛋白其复杂的变异性,说明恶性黑色素瘤细胞有许多种调节凋亡及产生凋亡不足的可能性。进一步理解这些分子信号蛋白的相互作用机制及参与调控凋亡的途径,认识他们在黑色素瘤细胞凋亡失调过程中的作用,识别黑色素瘤逃避凋亡刺激的不同路线,或许能为黑色素瘤提供一个新的预防、治疗方法。

Impaired ability to undergo apoptosis in response to a wide range of external stimuli acquires melanomas a selective advantage for progression and metastasis as well as their notorious resistance to therapy. Changes at genomic, transcriptional and post-translational levels of G-proteins and protein kinases （Ras） , their transcription factor effectors （c-jun, ATF2, stat3 and NF-kB） and upregulator of antiapoptosis gene （ Bcl-2, Bcl-XL, survivin, ML-IAP） affects apoptosis-induced of TNF, Fas and TRAIL receptors, which play important roles in acquiring melanoma＇ s resistance to apoptosis. The complexity of the molecular variants involved in signal transduction along apoptotic pathways suggests that the cell may have a variety of possibilities for regulating apoptosis and generating apoptosis deficiency.