A. M. Slonchak1, A. Chwieduk2, J. Rzeszowska-Wolny2, M. Yu. Obolenska1
1Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
2M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice;
Glutathione S-transferase P1 is a major phase II detoxification enzyme in most cell types. Aberrant expression of GSTP1 is associated with carcinogenesis and development of multidrug resistance. GSTP1 gene transcription is regulated by promoter methylation and by transcription factors. To elucidate the mechanisms responsible for the different levels of GSTP1 expression observed in Hbl-100 and BeWo cells we utilized truncated promoter constructs to compare the functional role of different promoter elements. We also identified transcription factors binding the responsive elements by electrophoretic mobility shift assay. The applied approaches provided the evidence that binding of transcription factors to ARE, CRE and NF-?B sites are responsible for the cell specific levels of GSTP1 expression in Hbl-100 and BeWo cells. It was also indicated that partial promoter methylation occurs in BeWo cells.
Key words: glutathione S-transferase P1, gene expression, carcinogenesis, promoter, DNA methylation, response element, transcription factors, transcription regulation.
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© The Ukrainian Biochemical Journal