Genetic alterations and expression of the protein phosphatase 1 genes in human cancers.
Recent studies have revealed that genetic alterations of the protein phosphatase genes, including PTEN, PPP2R1A, PPP2R1B and PPP1R3, are involved in human carcinogenesis. In the present study, we examined the genetic and expression status of nine protein phosphatase 1 (PP1) genes in 55 human cancer cell lines, consisting of 10 small cell lung cancers, 22 non-small cell lung cancers, 11 colorectal cancers, 7 gastric cancers and 5 ovarian cancers. The PP1 genes examined were three catalytic subunit genes, PPP1CA, PPP1CB and PPP1CC, and six regulatory subunit genes, PPP1R1A, PPP1R2, PPP1R5, PPP1R6, PPP1R7 and PPP1R8. Three catalytic subunit genes and three regulatory subunit genes, PPP1R2, PPP1R7 and PPP1R8, were ubiquitously expressed in the 55 cell lines, while PPP1R1A, PPP1R5, and PPP1R6 were differentially expressed. Possible missense mutations of the PPP1R5, PPP1R7 and PPP1R8 genes were detected in one (2%), two (4%) and one (2%) cell line, respectively. A rare, non-synonymous polymorphism was also identified in the PPP1R5 gene. Four of the 55 cell lines carried genetic alterations of several protein phosphatase genes, including PTEN, PPP1R3, PPP1R7 and PPP1R8. Ubiquitous expression as well as a lack of genetic diversity of catalytic subunit genes suggested the essential role of these genes for the growth of cancer cells. In contrast, differential expression, somatic mutations and/or genetic polymorphisms of several regulatory subunit genes indicate the involvement of these genes in multistep carcinogenesis.
Takakura
S
S
Biology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Kohno
T
T
Manda
R
R
Okamoto
A
A
Tanaka
T
T
Yokota
J
J
D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D054645:Protein Phosphatase 1; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D010744:Phosphoric Monoester Hydrolases