PPP1R3 gene (Protein phosphatase 1) alterations in colorectal cancers

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[Objective] Protein phosphatases are known to control various intracellular information such as intracellular signal transduction, cell cycling, and metabolic systems, through phosphorylation and dephosphorylation. Among the genes encoding them, the PPP1R3 gene is located on chromosome 7q31, and encodes protein phosphatase 1 (regulatory 3). It has recently been reported that the inactivation of various phosphatase proteins causes abnormalities of cell division and cell growth systems. This study analyzed mutations in the PPP1R3 gene.[Methods] Fifty patients with colorectal cancer who had uhdergone resection in our department were analyzed. DNA was extracted from normal tissue and primary lesions of colorectal cancer, and subjected to SSCP. DNA samples showing abnormal SSCP patterns were sequenced to analyze mutations in the PPP1R3 gene. Deletion mutants of exons containing mutations were prepared and assayed for intranuclear transcription activity.[Results] (1) SSCP analysis of PPP1R3 showed abnormal patterns in 6 (12%) of the 50 colorectal cancers. (2) DNA sequencing of the 6 samples showing abnormal SSCP patterns confirmed point mutations in exon 4 in 4 samples, and in exon 1 in 2 samples. (3) Enhancement of luciferase activity by the full PPP1R3 gene was confirmed. However, when deletion mutants of point mutation-containing exon 1 or exon 4 were examined for luciferase activity, enhancement of the activity was decreased in the exon 1 deletion mutants, and no enhancement of the activity was noted in the exon 4 deletion mutants.[Conclusion] Mutations in the PPP1R3 gene and their effects on intracellular transcription activity were observed in colorectal cancers. These findings suggest that protein phosphatase 1 (regulatory 3) protein is involved in intracellular processes in some colorectal cancers.