The mechanism of PPP2R1B genein colorectal cancers

背景：染色体11q区在结直肠癌中经常缺失。肿瘤抑制基因PPP2R1B编码丝氨酸/苏氨酸特异性蛋白磷酸酶β亚基β的亚型，位于11q22-23，在癌症患者中失活。方法：检测50例手术切除的结直肠癌组织中PPP2R1B基因的突变及其与PP2A-C蛋白的相互作用。结果：50例结直肠癌组织中PPP2R1B基因错义突变4例(8%)，β纯合缺失1例。结直肠癌组织中PPP2R1B基因第412-601位氨基酸序列(PP2A-C蛋白结合区)的缺失和/或点突变抑制了PP2A-Aβ和PP2A-C蛋白的免疫共沉淀。结论：PPP2R1B基因作为肿瘤抑制基因发挥作用，并作为分子开关对特定的上游信号作出反应。一旦激活，该基因会改变特定下游靶蛋白的活性，以调节某些结直肠癌的细胞周期和/或新陈代谢。

Background : The chromosome region 11q is frequently deleted in colorectal cancers. The PPP2R1B tumor suppressor gene, encoding the β isoform of the A subunit of serine/threonine-specific protein phosphatase 2A (PP2A-Aβ), located at 11q22-23, is inactivated in patients with cancer. The present study determines whether or not PP2A-Aβ is altered in colorectal cancers.Method : We searched for alterations of the PPP2R1B gene and interactions between PP2A-Aβ and PP2A-C proteins in 50 surgically resected colorectal cancer tissues.Results : Missense mutations and homozygous deletions of the PPP2R1B gene were found in four of 50 patients (8 %) and in one of 50 patients, respectively, with colorectal cancers. Deletions and/or point mutations within 412-601 amino acid sequences (binding regions of PP2A-C protein) of the PPP2R1B gene derived from colorectal cancer tissues inhibited co-immunoprecipitation of PP2A-Aβ and PP2A-C proteins.Conclusion : These finding suggest that the PPP2R1B gene functions as a tumor suppressor gene and acts as a molecular switch that becomes active in response to specific upstream signals. Upon activation, the gene alters the activities of specific downstream target proteins for the cell cycle regulations and/or metabolism in some colorectal cancers.