Constitutive activation of transcription factor AP-2 is associated with decreased MnSOD expression in transformed human lung fibroblasts.
Activator protein-2 (AP-2) is a transcription factor with transactivating and transrepressing potential in different promoter contexts. AP-2 contains seven cysteines, and its in vitro DNA binding activity is redox-sensitive. Superoxide dismutase-2 (SOD2), which encodes the antioxidant enzyme manganese superoxide dismutase (MnSOD), is a putative tumor suppressor gene whose loss of expression is associated with the malignant phenotype. SOD2 promoter mutations that generate new AP-2 sites are associated with loss of MnSOD expression in cancer cells. In the current study, we have identified an inverse expression pattern between AP-2 and MnSOD in normal versus transformed human cells. MRC5 cells are a normal human lung fibroblast cell strain that is mortal and senesces after a certain number of passages in vitro. MRC5-VA is a simian virus transformed variant of MRC5. We determined the levels of expression of MnSOD and AP-2 in these two cell types at the levels of mRNA, protein, and activity. Our results indicated that MnSOD expression was significantly decreased in MRC5-VA cells compared with MRC5 cells at each level of investigation, whereas AP-2 showed an opposing pattern of expression and DNA binding activity. These results suggest that AP-2 may participate in the mechanism(s) underlying decreased expression of SOD2 in transformed cells.
Zhu
C
C
Department of Radiology, The University of Iowa, Iowa City 52242, USA.
Huang
Y
Y
Weydert
C J
CJ
Oberley
L W
LW
Domann
F E
FE
D015152:Blotting, Northern; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D013539:Simian virus 40 / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000099156:Superoxide Dismutase 2
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2