title: Differential regulation of TP73 isoforms by 1α,25-dihydroxyvitamin D3 and survivin in human colon and breast carcinomas.
abstract: We evaluate whether 1,25(OH)(2)D(3) downregulates TP73 variants in colon and breast carcinomas, the role of survivin in this context, and the significance of this network in the clinic. Tumor cells were treated/untreated with 1,25(OH)(2)D(3) and transiently transfected with survivin. Levels of survivin and TP73 variants were evaluated by quantitative RT-PCR and Western blotting. In 75 colon and 60 breast cancer patients, the expressions of survivin and TP73 isoforms were determined. Tumor characteristics were examined in each patient. Survivin protein levels were also evaluated in a subgroup of patients and cell lines. Decrease in survivin and TAp73 transcripts and protein and ΔNp73 mRNA was detected after 1,25(OH)(2)D(3) treatment. Ectopic survivin expression led to an increase in the TAp73, ΔNp73, ΔEx2p73, and ΔEx2-3p73 transcripts. In cancer patients, direct correlations were observed between TP73 variants and survivin levels. 1,25(OH)(2)D(3) negatively regulate survivin and TP73 variants in colon and breast cancer cells. Positive regulation of TP73 isoforms by survivin may exist, which reinforces the possibility that the downregulation of TP73 forms by 1,25(OH)(2)D(3) is survivin-dependent.
authors.affiliation: Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, C/ Manuel de Falla 1, Majadahonda, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Díaz
authors.forename: José M
authors.initials: JM
authors.lastname: González-Sancho
authors.forename: Beatriz
authors.initials: B
authors.lastname: Soldevilla
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.forename: José M
authors.initials: JM
authors.lastname: García
authors.forename: Vanesa
authors.initials: V
authors.lastname: García
authors.forename: Cristina
authors.initials: C
authors.lastname: Peña
authors.forename: Mercedes
authors.initials: M
authors.lastname: Herrera
authors.forename: Irene
authors.initials: I
authors.lastname: Gómez
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
authors.forename: Gemma
authors.initials: G
authors.lastname: Domínguez
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000077022:Survivin; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D000077022:Survivin; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; D002117:Calcitriol