The mechanism of PPP2R1B genein colorectal cancers

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Fukui Medical University
• Principal Investigator: GOI Takanori Fukui Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (60225638)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Akio Fukui Medical University, Faculty of Medicine, Professor, 医学部, 教授 (10174608)
• Project Period (FY): 2001 – 2002
• Keywords: PPP2R1B gene / Protein phosphatase / PP2A protein / colorectal cancer

Research Abstract

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.