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Alterations of the PPP1R3 gene in human cancer
T Kohno1, S Takakura, T Yamada
1Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
Recently, the PTEN/MMAC1 gene encoding a protein phosphatase (PP) and the PPP2R1B gene encoding a regulatory subunit of PP2A have been identified as being genetically altered in several types of human cancers, indicating that aberrations of intracellular signaling pathways via PPs are involved in human carcinogenesis. Here we report genetic alterations of the PPP1R3 gene located at chromosome 7q31, which encodes regulatory subunit 3 of PP1, in various types of human cancers. Mutations of the PPP1R3 gene were detected in 5 of 33 (15%) non-small cell lung cancer cell lines and 2 of 38 (5%) primary non-small cell lung cancers and were also observed in cell lines derived from a small cell lung cancer, an ovarian cancer, a colorectal cancer, and a gastric cancer. Mutations were widely dispersed in the coding region of the PPP1R3 gene. Three of the 11 detected mutations were nonsense mutations, whereas the remaining ones were missense mutations, most of which caused substitutions of evolutionarily conserved amino acids. These findings suggest that PPP1R3 alteration plays a role in the development of human cancers and that PPP1R3 could act as a tumor suppressor gene.
Insights
Genetic alterations in the PPP1R3 gene, encoding a protein phosphatase 1 (PP1) regulatory subunit, were found in multiple human cancers. These mutations suggest PPP1R3 may function as a tumor suppressor gene in carcinogenesis.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Protein phosphatases (PPs) play roles in intracellular signaling pathways implicated in human carcinogenesis.
- Genetic alterations in PTEN/MMAC1 and PPP2R1B genes suggest involvement of PPs in cancer development.
Purpose of the Study:
- To investigate genetic alterations of the PPP1R3 gene, encoding a regulatory subunit of protein phosphatase 1 (PP1), in various human cancers.
- To determine the potential role of PPP1R3 gene alterations in human carcinogenesis.
Main Methods:
- Screening for mutations in the PPP1R3 gene across cancer cell lines and primary tumor samples.
- Analysis of mutation types (nonsense, missense) and their locations within the coding region.
- Assessment of amino acid conservation at mutation sites.
Main Results:
- Genetic alterations (mutations) in the PPP1R3 gene were detected in non-small cell lung cancer cell lines (15%) and primary tumors (5%).
- Mutations were also identified in cell lines from small cell lung cancer, ovarian, colorectal, and gastric cancers.
- Detected mutations included nonsense and missense types, with many affecting conserved amino acids.
Conclusions:
- Alterations in the PPP1R3 gene are associated with the development of diverse human cancers.
- The PPP1R3 gene is proposed to function as a tumor suppressor gene.
- Further research into PPP1R3's role in cancer is warranted.