Effects of silencing of mutant p53 gene in human lung adenocarcinoma cell line Anip973.

The mutational spectrum of p53 gene and the biological effects of mutant p53 protein vary greatly from one type of tumor to another. To investigate the biological effects of mutant p53 gene in human lung adenocarcinoma, mutant p53 was silenced by RNA interference (RNAi) in cell line Anip973. Then, the effects of mutant p53 silencing on cell cycle distribution and regulators, and on the TGFbeta/BMP signaling pathway were then investigated by flow cytometry, RT-PCR, and cDNA array screening. This study showed that mutant p53 silencing in Anip973 resulted in G1 arrest and G2/M arrest, for which the increased expression of p27 gene might be an important contribution factor. It was also found that the absence of mutant p53 affected the signal transduction of TGFbeta/BMP pathway mainly by up-regulating the expression of BMP superfamily cytokine growth differentiation factor 9 (GDF9), activin superfamily cytokine inhibin beta B (INHBB), smads target genes insulin-like growth factor binding protein 3 (IGFBP3) and involucrin (IVL). These results indicated the basic mechanism and the significant effects of mutant p53 on specific biological processes such as cell cycle and signal transduction in lung adenocarcinoma. These activities of mutant p53 may contribute to its 'gain of function' effects, which accelerate the oncogenesis and promotion of the tumor.