tailieunhanh - Báo cáo khoa học: Sp1 binds to the external promoter of the p73 gene and induces the expression of TAp73c in lung cancer

Thep73 gene possesses an extrinsic P1 promoter and an intrinsic P2 promoter, resulting in TAp73 andDMp73 isoforms, respectively. The ulti-mate effect ofp73in oncogenesis is thought to depend on the apoptotic TA to antiapoptoticDN isoforms’ ratio. | Sp1 binds to the external promoter of the p73 gene and induces the expression of TAp73c in lung cancer Stella Logotheti1 loannis Michalopoulos2 Maria Sideridou3 Alexandros Daskalos4 Sophia Kossida2 Demetrios A. Spandidos5 John K. Field4 Borek Vojtesek6 Triantafyllos Liloglou4 Vassilis Gorgoulis3 and Vassilis Zoumpourlis1 1 BiomedicalApplications Unit Institute of BiologicalResearch and Biotechnology NationalHellenic Research Foundation Athens Greece 2 Bioinformatics MedicalInformatics Foundation for BiomedicalResearch of the Academy of Athens Greece 3 Molecular Carcinogenesis Group Department of Histology and Embryology MedicalSchoolof Athens Greece 4 Roy Castle Lung Cancer Research Programme Division of Surgery and Oncology University of LiverpoolCancer Research Centre University of Liverpool UK 5 Laboratory of ClinicalVirology Faculty of Medicine University of Crete Heraklion Greece 6 Department of Oncologicaland ExperimentalPathology Masaryk MemorialCancer Institute Brno Czech Republic Keywords lung cancer P1 promoter p73 isoforms Sp1 TAp73c ANp73 Correspondence V. Zoumpourlis BiomedicalApplication Unit Institute of Biological Research and Biotechnology NationalHellenic Research Foundation 48 Vas. Constantinou Ave 116 35 Athens Greece Fax 210 7273677 Tel 210 7273730 E-mail vzub@ Received 16 February 2010 revised 1 May 2010 accepted 12 May 2010 doi The p73 gene possesses an extrinsic P1 promoter and an intrinsic P2 promoter resulting in TAp73 and ANp73 isoforms respectively. The ultimate effect of p73 in oncogenesis is thought to depend on the apoptotic TA to antiapoptotic AN isoforms ratio. This study was aimed at identifying novel transcription factors that affect TA isoform synthesis. With the use of bioinformatics tools in vitro binding assays and chromatin immunoprecipitation analysis a region extending -233 to -204 bp upstream of the transcription start site of the human p73 P1 promoter containing conserved Sp1-binding