Of the three GOF mechanism models with mutant p53, direct and indirect transcription regulations are involved, which enable cells to gain oncogenic functions and proliferation advantages. However, the underlying mechanism of GOF is still unclear. In p53 mouse models, p53 missense mutations produce more aggressive and metastatic tumors compared to p53 null or heterozygous mice, suggesting that GOF is the key characteristic of mutant p53. Mutant p53 also can confer anti-apoptotic ability on tumor cells, thus promoting carcinogenesis and drug resistance, and causing poor patient prognosis. More than 50% of human cancer types harbor missense mutations in TP53, and some mutant p53 proteins have lost the function of wild-type p53 protein (loss of function, LOF) and gained the oncogenic function (gain of function, GOF) in promoting migration, invasion, and metastasis of cancer cells.
TP53 ( Trp53 in mouse) is a critical tumor suppressor gene encoding p53 protein and an essential transcription factor that regulates cell cycle arrest, apoptosis, and senescence.
SsGSEA, single sample gene set enrichment analysis ChIP-chip, chromatin immunoprecipitation-on-chip
0 kommentar(er)
