title: DAX1 Overexpression in Pediatric Adrenocortical Tumors: A Synergic Role with SF1 in Tumorigenesis.
abstract: DAX1 transcription factor is a key determinant of adrenogonadal development, acting as a repressor of SF1 targets in steroidogenesis. It was recently demonstrated that DAX1 regulates pluripotency and differentiation in murine embryonic stem cells. In this study, we investigated DAX1 expression in adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34 children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30 carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real-time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34) and 24% (17 out of 70) of pediatric and adult ACTs, respectively (χ(2)=10.1, p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5-4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with functional status in ACTs. Interestingly, a positive correlation was observed between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55 for each group separately; p<0.0001). In addition, DAX1 gene expression was significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In conclusion, DAX1 strong protein expression was more frequent in pediatric than in adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs, suggesting that these transcription factors might cooperate in adrenocortical tumorigenesis.
authors.affiliation: Unidade de Suprarrenal & Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular (Laboratório de Investigação Medica, LIM 42) da Disciplina de Endocrinologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: G R V
authors.initials: GR
authors.lastname: de Sousa
authors.affiliation: Hospital do Câncer de Barretos, RO, Brazil.
authors.forename: I C
authors.initials: IC
authors.lastname: Soares
authors.affiliation: Unidade de Suprarrenal & Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular (Laboratório de Investigação Medica, LIM 42) da Disciplina de Endocrinologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Faria
authors.affiliation: Divisão de Anatomia Patologia, Laboratório de Patologia Hepática/LIM14 do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil.
authors.forename: V B
authors.initials: VB
authors.lastname: Domingues
authors.affiliation: Divisão de Anatomia Patologia, Laboratório de Patologia Hepática/LIM14 do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Wakamatsu
authors.affiliation: Unidade de Suprarrenal & Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular (Laboratório de Investigação Medica, LIM 42) da Disciplina de Endocrinologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Lerario
authors.affiliation: Divisão de Anatomia Patologia, Laboratório de Patologia Hepática/LIM14 do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil.
authors.forename: V A F
authors.initials: VA
authors.lastname: Alves
authors.affiliation: Divisão de Anatomia Patologia, Laboratório de Patologia Hepática/LIM14 do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil.
authors.forename: M C N
authors.initials: MC
authors.lastname: Zerbini
authors.affiliation: Unidade de Suprarrenal & Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular (Laboratório de Investigação Medica, LIM 42) da Disciplina de Endocrinologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: B B
authors.initials: BB
authors.lastname: Mendonca
authors.affiliation: Unidade de Suprarrenal & Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular (Laboratório de Investigação Medica, LIM 42) da Disciplina de Endocrinologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: M C B V
authors.initials: MC
authors.lastname: Fragoso
authors.affiliation: Unidade de Suprarrenal & Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular (Laboratório de Investigação Medica, LIM 42) da Disciplina de Endocrinologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Latronico
authors.affiliation: Unidade de Suprarrenal & Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular (Laboratório de Investigação Medica, LIM 42) da Disciplina de Endocrinologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: M Q
authors.initials: MQ
authors.lastname: Almeida
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism*; D018246:Adrenocortical Adenoma / Q000235:genetics / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; C539965:NR0B1 protein, human; C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1