Alterations of the PPP1R3 gene in human cancer

Recently, the PTEN/MMAC1 gene encoding a protein phosphatase (PP) and the P PP2R1B gene encoding a regulatory subunit of PP2A have been identified as b eing genetically altered in several types of human cancers, indicating that aberrations of intracellular signaling pathways via PPs are involved in hu man carcinogenesis. Here we report genetic alterations of the PPP1R3 gene l ocated at chromosome 7q31, which encodes regulatory subunit 3 of PP1, in va rious 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%) prima ry 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 sugge st that PPP1R3 alteration plays a role in the development of human cancers and that PPP1R3 could act as a tumor suppressor gene.