title: The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age.
abstract: The regulation of insulin-like growth factor-binding protein 3 (IGFBP3) gene expression is complex, because it can be induced by agents that both stimulate and inhibit the proliferation. The principal aim of this study was to investigate whether p73, a member of the p53 gene family, has a role in the regulation of the IGFBP3 expression and whether this regulation occurs in a context of cell survival or death. We demonstrate that IGFBP3 is a direct TAp73α (the p73 isoform that contains the trans-activation domain) target gene and activates the expression of IGFBP3 in actively proliferating cells. As IGFBP3 plays a key role in regulating the growth hormone/insulin-like growth factor type 1 (GH/IGF1) axis, whose alterations in gene expression appear to have a role in the growth failure of children born small for gestational age (SGA), we measured the mRNA expression levels of p73 and IGFBP3 in a group of SGA children. We found that mRNA expression levels of p73 and IGFBP3 are significantly lower in SGA children compared with controls and, in particular, p73 mRNA expression is significantly lower in SGA children with respect to height. Our results shed light on the intricate GH/IGF pathway, suggesting p73 as a good biomarker of the clinical risk for SGA children to remain short in adulthood.
authors.affiliation: Institute for Biomedical Technologies-ITB, National Research Council-Bari, 70126 Bari, Italy.
authors.forename: Flaviana
authors.initials: F
authors.lastname: Marzano
authors.affiliation: Section of Pediatrics, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," 70124 Bari, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ventura
authors.affiliation: Institute for Biomedical Technologies-ITB, National Research Council-Bari, 70126 Bari, Italy.
authors.forename: Mariano Francesco
authors.initials: MF
authors.lastname: Caratozzolo
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "A. Moro," 70126 Bari, Italy.
authors.forename: Italia
authors.initials: I
authors.lastname: Aiello
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "A. Moro," 70126 Bari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mastropasqua
authors.affiliation: Section of Human Anatomy and Histology, Department of Basic and Medical Sciences, Neurosciences and Sense Organs, University of Bari "A. Moro," 70124 Bari, Italy.
authors.forename: Giacomina
authors.initials: G
authors.lastname: Brunetti
authors.affiliation: Section of Pediatrics, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," 70124 Bari, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Cavallo
authors.affiliation: Institute for Biomedical Technologies-ITB, National Research Council-Bari, 70126 Bari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Sbisà
authors.affiliation: Section of Pediatrics, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," 70124 Bari, Italy apollonia.tullo@ba.itb.cnr.it mariafelicia.faienza@uniba.it.
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Faienza
authors.affiliation: Institute for Biomedical Technologies-ITB, National Research Council-Bari, 70126 Bari, Italy apollonia.tullo@ba.itb.cnr.it mariafelicia.faienza@uniba.it.
authors.forename: Apollonia
authors.initials: A
authors.lastname: Tullo
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016158:Genes, p53; D045325:HCT116 Cells; D057809:HEK293 Cells; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D019382:Human Growth Hormone