Abstract
APE1 and several other Base Excision Repair (BER) proteins are known to be phosphorylated, which may regulate their activity and expression. PIN1 is a proline isomerase that acts on proteins phosphorylated at serine/threonine‐proline motifs. Its impact on conformation can affect protein function and turnover. Here we investigated the effect of PIN1 depletion on APE1 expression in mammary tumors. EMT6 murine mammary adenocarcinoma cells lacking PIN1 were generated by stable knockdown with small hairpin RNA. Parallel control cells were established using a mutant sequence. Tumors were established by injecting cells in the 4th mammary fat pad of female BALB/c mice. Tumors lacking PIN1 grew faster and had significantly higher APE1 levels than the corresponding slower growing control tumors. To determine if APE1 expression was attributable to tumor size or PIN1 deficiency, knockdown and control tumors were harvested at different times and tumors of similar sizes were compared. PIN1 knockdown tumors again had significantly higher levels of APE1 than control tumors of similar size harvested slightly later. These results suggest that suppression of PIN1 increases APE1 synthesis or reduces its degradation in developing tumors in vivo. PIN1 may regulate the sensitivity of tumors to DNA damaging agents by its effect on this BER enzyme.
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