Hayashida Yuichi, Goi Takanori, Hirono Yasuo, Katayama Kanji, Urano Takeshi, Yamaguchi Akio
First Department of Surgery, University of Fukui, 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Oncol Rep. 2005 Jun;13(6):1223-7.
The PPP1R3 gene is located on chromosome 7q31, and encodes protein phosphatase 1 (regulatory 3). It has been reported that the inactivation of various phosphatase proteins causes abnormalities in cell division and cell growth systems. We analyzed alterations in the PPP1R3 gene and its relationship to tumor progression and metastasis. Deletion mutants of exons containing mutations were prepared and assayed for intranuclear transcription activity. SSCP analysis of PPP1R3 showed abnormal patterns in 6 (12%) of the 50 colorectal cancers. 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. PPP1R3 gene alterations correlated with lymph node and liver metastases. Enhancement of luciferase activity by the full PPP1R3 gene was confirmed. However, when point mutation-containing exon 1 or 4 deletion mutants were examined for luciferase activity, enhancement of activity was decreased in the exon 1 deletion mutants, while no enhancement of the activity was noted in the exon 4 deletion mutants. These findings suggest that protein phosphatase 1 (regulatory 3) protein is involved in intracellular processes in some colorectal cancers and may play a role in metastasis.
PPP1R3基因位于7号染色体的7q31上，编码蛋白磷酸酶1（调节亚基3）。据报道，各种磷酸酶蛋白的失活会导致细胞分裂和细胞生长系统异常。我们分析了PPP1R3基因的改变及其与肿瘤进展和转移的关系。制备了含有突变的外显子缺失突变体，并检测其核内转录活性。对PPP1R3进行的单链构象多态性（SSCP）分析显示，在50例结直肠癌中有6例（12%）呈现异常模式。对显示SSCP异常模式的6个样本进行DNA测序，证实4个样本的外显子4存在点突变，2个样本的外显子1存在点突变。PPP1R3基因改变与淋巴结和肝转移相关。证实了完整的PPP1R3基因可增强荧光素酶活性。然而，当检测含有点突变的外显子1或外显子4缺失突变体的荧光素酶活性时，外显子1缺失突变体的活性增强降低，而外显子4缺失突变体未观察到活性增强。这些发现表明，蛋白磷酸酶1（调节亚基3）蛋白在某些结直肠癌的细胞内过程中起作用，可能在转移中发挥作用。
