Subtraction hybridization identifies a transformation progression-associated gene PEG -3 with sequence homology to a growth arrest and DNA damage-inducible gene
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Media type:
E-Article
Title:
Subtraction hybridization identifies a transformation progression-associated gene PEG -3 with sequence homology to a growth arrest and DNA damage-inducible gene
Contributor:
Su, Zao-Zhong;
Shi, Yijie;
Fisher, Paul B.
imprint:
Proceedings of the National Academy of Sciences, 1997
Published in:Proceedings of the National Academy of Sciences
Description:
<jats:p>
Cancer is a progressive multigenic disorder characterized by defined changes in the transformed phenotype that culminates in metastatic disease. Determining the molecular basis of progression should lead to new opportunities for improved diagnostic and therapeutic modalities. Through the use of subtraction hybridization, a gene associated with transformation progression in virus- and oncogene-transformed rat embryo cells, progression elevated gene-3 (PEG-3), has been cloned.
<jats:italic>PEG-3</jats:italic>
shares significant nucleotide and amino acid sequence homology with the hamster growth arrest and DNA damage-inducible gene
<jats:italic>gadd34</jats:italic>
and a homologous murine gene,
<jats:italic>MyD116</jats:italic>
, that is induced during induction of terminal differentiation by interleukin-6 in murine myeloid leukemia cells.
<jats:italic>PEG-3</jats:italic>
expression is elevated in rodent cells displaying a progressed-transformed phenotype and in rodent cells transformed by various oncogenes, including Ha-
<jats:italic>ras</jats:italic>
, v-
<jats:italic>src</jats:italic>
, mutant type 5 adenovirus (Ad5), and human papilloma virus type 18. The
<jats:italic>PEG-3</jats:italic>
gene is transcriptionally activated in rodent cells, as is
<jats:italic>gadd34</jats:italic>
and
<jats:italic>MyD116</jats:italic>
, after treatment with DNA damaging agents, including methyl methanesulfonate and γ-irradiation. In contrast, only
<jats:italic>PEG-3</jats:italic>
is transcriptionally active in rodent cells displaying a progressed phenotype. Although transfection of
<jats:italic>PEG-3</jats:italic>
into normal and Ad5-transformed cells only marginally suppresses colony formation, stable overexpression of
<jats:italic>PEG-3</jats:italic>
in Ad5-transformed rat embryo cells elicits the progression phenotype. These results indicate that
<jats:italic>PEG-3</jats:italic>
is a new member of the
<jats:italic>gadd</jats:italic>
and
<jats:italic>MyD</jats:italic>
gene family with similar yet distinct properties and this gene may directly contribute to the transformation progression phenotype. Moreover, these studies support the hypothesis that constitutive expression of a DNA damage response may mediate cancer progression.
</jats:p>