Abstract
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.
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