Dihydrodiol dehydrogenases are a family of aldo-keto reductases (AKR1Cs) involved in the metabolism of steroid hormones and xenobiotics. Here, we have cloned and characterized the proximal promoter region of the human AKR1C1 gene. The 5′ flanking proximal promoter region of the AKR1C1 gene consists of a TATA box and an inverted CCAAT binding site. Deletion analysis of the 5′-flanking, ∼3.0 kb region of the human AKR1C1 gene, identified the region between −128 to −88 as the minimal proximal promoter that is essential for basal transcription of AKR1C1 in human ovarian (2008 & 2008/C13*), lung (H23 & A549) and liver carcinoma (HepG2) cells. Based on computational analysis, a set of potential putative transcription factor binding sites for Oct1, Sp1, NF-Y, C/EBP, p40X, USF, NF1 and AP-2 were identified in this region. Site-directed mutagenesis studies indicated that the transcription factor binding sites for NF-Y/CEBP were essential for controlling the basal transcription of AKR1C1 in all the cancer cells studied. Electrophoretic mobility shift (EMSAs) and gel supershift assays demonstrated that the transcription factor NF-Y preferentially binds to the inverted CCAAT box at −109ATTGG−105 of the AKR1C1 gene. These results indicate that the NF-Y transcription factor regulates the basal transcription of AKR1C1 in human ovarian, lung and liver carcinoma cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4990.