Premium
Progression elevated gene‐3, PEG‐3 , induces genomic instability in rodent and human tumor cells
Author(s) -
Su Zaozhong,
Gopalkrishnan Rahul V.,
Narayan Gopeshwar,
Dent Paul,
Fisher Paul B.
Publication year - 2002
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10114
Subject(s) - biology , genome instability , ectopic expression , microbiology and biotechnology , gene expression , gene , cancer cell , tumor progression , transgene , cancer , phenotype , cancer research , genetics , dna damage , dna
Abstract Genomic instability is a fundamental component of cancer progression. Subtraction hybridization identified a novel rodent gene, progression elevated gene‐3 ( PEG‐3 ) whose expression directly correlates with cancer aggressiveness and progression. Moreover, ectopic expression of PEG‐3 in rodent or human tumor cells produces an aggressive transformed phenotype. We demonstrate that PEG‐3 expression in rodent tumor cells correlates directly with genomic instability as characterized by alterations in chromosome composition and structure. Additionally, elevated endogenous or ectopic expression of PEG‐3 in rodent and human tumor cells, respectively, enhances gene amplification, as monitored by resistance to methothrexate (MTX) and amplification of the dihydrofolate reductase ( dhfr) gene. Stable expression of PEG‐3 in normal cloned rat embryo fibroblast (CREF) cells marginally elevates MTX resistance, but morphology remains unaltered and anchorage independence is not induced, suggesting that these phenotypes are separable in immortal cells and gene amplification may precede the acquisition of morphological and oncogenic transformation. The present studies document that stable, inducible, and transient expression of PEG‐3 in cancer cells augments genomic instability. In these contexts, one mechanism by which PEG‐3 influences cancer progression may be by preferentially facilitating the development of genomic changes in evolving cancer cells. © 2002 Wiley‐Liss, Inc.