前列腺癌中TMPRSS2-ETS基因融合及机制研究进展

超过50%的前列腺癌中存在跨膜丝氨酸蛋白酶2(TMPRSS2)和E26(ETS)转录因子间的基因融合,其中TMPRSS2-ERG最为常见。TMPRSS2-ERG基因融合造成的ERG过表达参与了前列腺的癌变。雄激素受体结合和遗传毒性胁迫共同诱导了染色体的靠近和TMPRSS2-ETS的基因融合。TMPRSS2-ERG基因融合可作为前列腺癌诊断的一种生物标志物,并可通过病人尿液检测来实现。文章对TMPRSS2-ETS基因融合的特征、融合及致癌及临床应用进行了综述。     

Human ETS1 oncoprotein. Purification, isoforms, -SH modification, and DNA sequence-specific binding.

The human ETS1 proto-oncogene proteins have been isolated from the T-cell leukemia line, CEM, by immunoaffinity chromatography and their identity confirmed by NH2-terminal amino acid sequencing. Incubation of CEM cells with N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) indicates that ETS proteins can be modified in their cellular context and that pretreatment of the cells with N-ethylmaleimide (NEM) protects ETS1 proteins from TLCK modification. These data show that ETS1 proteins can exist in at least two different states, -SH-available and -SH-protected. Renatured human ETS1 has DNA sequence-specific binding to the PEA3 (CAGGAAGT) motif. The ETS1.PEA3 complex can be observed by electrophoretic mobility shift assays (EMSA). Purified ETS1 retards a band which is exactly the same size as a complex that is retarded from nuclear extracts prepared from CEM cells. Reduced ETS1 is required to form the ETS1.PEA3 complex, however; modification of the ETS1 -SH groups by either NEM or by TLCk does not inhibit formation of the complex. The ETS1.PEA3 complex formed with TLCK-modified ETS1 has a slower mobility than the complex formed with unmodified ETS1. Zone sedimentation analysis of purified ETS1 indicates that it is the monomer of ETS1 which binds to the PEA3 oligonucleotide.