REGγ Mediate The Expression Of P53Downstream Genes And The"Gain Of Function" Of Mutant P53

Since the proteasome activator REGy is reported to have the ability of degrading the intact proteins in the cell, such as SRC3and p21, the function of REGy has been researched much more deep and extensive than before. Among which REGy in the tumor genesis and development attract the most attention.Previously, we used the bioinformatics methods to predict the key genes in the REGy and cancer signaling pathway. In this paper, at the molecular level, we detected the gene expression by the Real-time PCR technique, meanwhile, at the tissue level, by the Immunohistochemical technique. Finally, we found that the expression patterns of most key genes are consistent with the results predicted by the bioinformatics methods.By using the immunohistochemical method, we found that REGy is widely expressed in varieties of tumors, including ovarian cancer, gastric cancer, kidney cancer and other uncommon cancers. We also confirmed REGy is highly expressed in the thyroid neoplasms, colorectal cancer, breast cancer, lung cancer, which are consistent with the research done before. Therefore, REGy can be used as the indicator for future clinical detection of tumor.At the same time, the results of IHC on different types of cancer showed that p53and REGy expression have correlation both on the co-localization and on the expression level. This result gave us a hint that as a transcription factor, p53may regulate the expression of REGy. The mechanism researches are still undergoing.In the study of the regulatory function of p53protein, we also found there are some crosstalk between p53and TGFβ signaling pathway.Transforming growth factor is a quite essential growth-inhibitory cytokine, but growth inhibition is only one of its many effects. TGF(3and other members of its family control many fundamental aspects of cellular behaviour, including migration, adhesion, differentiation and modification of the microenvironment. The loss of TGFβ receptor or SMAD functions accounts for a relatively small proportion of cases in which tumour cells become resistant to TGFβ mediated cytostasis or apoptosis. Missense mutations in the p53gene are commonly selected for in developing, human cancer cells. These diverse mutations in p53can inactivate its normal sequence-specific DNA-binding and transactivation function, but these mutations can also stabilize a mutant form of p53with pro-oncogenic potential. Mutant p53can antagonize the TGFβ mediates transcriptional regulation, mainly because when mutant p53interact with Smad3on MH2domain to form complex and combine to the promotor of the TGFβ target genes, lead to the antagonistic effect on the TGFβ caused growth inhibition. At the same time, mutant p53can upregulate the expression of slug, which is a key molecular in the epithelial mesenchymal transition. Slug can downregulate the expression of associated molecules in cell-cell junctions, while upregulate the expression of several "transfer machine", such as matrix metalloproteinase MMP, which makes the cell become more invasive. Here,in this study, we used some molecular methods to demonstrate the gain of function of mutant p53(GOF) by antagonize the signaling pathway MAPK, and then verified this hypothsis by detecting the key proteins markers'correlationship between mutant p53protein and cell migration,and between mutant p53protein MAPK signaling pathways. These results provide a favorable evidence for the inquiry of p53's new functions.