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Loss of Protein Phosphatase 2A Expression Correlates with Phosphorylation of DP-1 and Reversal of Dysplasia through Differentiation in a Conditional Mouse Model of Cancer Progression

¹ Graduate Program in Human Genetics
² University of Maryland School of Medicine, University of Maryland at Baltimore, Baltimore, Maryland;
³ Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland;
⁴ Lombardi Cancer Center, Department of Oncology, Georgetown University, Washington, DC

A conditional mouse model of time-dependent dysplasia reversal demonstrated that reversal and differentiation of dysplastic salivary gland tissue at the 4-month reversible stage was characterized by the appearance of a phosphorylated slower mobility form of Differentiation Related Transcription Factor 1-polypeptide-1 that was correlated with cellular differentiation. The phosphorylated form of DP-1 was not found at the 7-month irreversible stage or in adenocarcinomas. At the 4-month reversible stage, protein phosphatase 2A expression was down-regulated coincident with loss of oncogene expression, whereas PP2A expression persisted at the 7-month irreversible stage. Results are consistent with the hypothesis that persistent PP2A expression prevented the appearance of the phosphorylated form of DP-1 required for cellular differentiation and reversal of dysplasia after loss of oncogene expression.

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