Andriy Slonchak » Публикация

Аннотация The thesis is devoted to study of the cell-specific role of cis- and trans-acting factor in regulation of GSTP1 gene transcription in three malignant cell lines (breast cells Hbl-100, melanoma cells Me45 and choriocarcinoma cells BeWo), which possess different levels of GSTP1 expression and identification of changes in transcriptional regulation associated with neoplastic transformation of trophoblast cells. ARE and NF-κB sites were identified as positive and CRE and NF-κB-like site as negative regulatory elements. Proteins interacting with these sites were also identified. We demonstrated that CRE and NF-κB sites are responsible for cell-specific regulation of the GSTP1 transcription. The mode of ERβ and Fos interaction together with Jun binding mediates cell-specific influence of CRE and subunit composition of NF-κB is responsible for cell-specific action of NF-κB site. It was indicated that down-regulation of GSTP1 during placental carcinogenesis occurs due to lack of Jun in CRE-protein complex. We also demonstrated that in cells with transcription factor-mediated GSTP1 repression promoter of this gene undergoes methylation.