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.
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.
Tilli
Maddalena T
MT
Graduate Program in Human Genetics, University of Maryland at Baltimore, Baltimore, MD, USA.
Hudgins
Shawnté L
SL
Frech
M Silvina
MS
Halama
Ewa D
ED
Renou
Jean-Pierre
JP
Furth
Priscilla A
PA
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013363:Submandibular Gland / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C493736:Tfdp1 protein, mouse; D050680:Transcription Factor DP1; D014157:Transcription Factors; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2