Reduced Expression of Mismatch Repair Genes MSH6/MSH2 Directly Promotes Pituitary Tumor Growth via the ATR-Chk1 Pathway

错配修复基因 MSH6/MSH2 表达降低通过 ATR-Chk1 通路直接促进垂体瘤生长

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Conclusion

Reduction of MSH6 and MSH2 expression at the messenger RNA and protein levels could be involved in direct PA proliferation by promoting cell-cycle progression or decreasing the rate of apoptosis through interference with the function of the ATR-Chk1 pathway.

Results

Expression of mutS homologs 6 and 2 (MSH6 and MSH2) was positively associated with TVDT (R = 0.52, P = 0.003, and R = 0.44, P = 0.01), as were the corresponding protein levels. Gene expression was positively associated with ATR expression (R = 0.47, P < 0.00001, and R = 0.49, P < 0.00001). In AtT-20ins, the reduction of MSH6 and/or MSH2 expression by small interfering RNA significantly promoted cell proliferation by decreasing ATR expression. This effect was also observed in primary culture.

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