DAX1 Overexpression in Pediatric Adrenocortical Tumors: A Synergic Role with SF1 in Tumorigenesis

Author(s):Show less -

de Sousa, G. R. V. ^[1] ; Soares, I. C. ^[2] ; Faria, A. M. ^[1] ; Domingues, V. B. ^[3] ; Wakamatsu, A. ^[3] ; Lerario, A. M. ^{[1, 4]} ; Alves, V. A. F. ^[3] ; Zerbini, M. C. N. ^[3] ; Mendonca, B. B. ^[1] ; Fragoso, M. C. B. V. ^{[1, 4]} ; Latronico, A. C. ^[1] ; Almeida, M. Q. ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Hosp Clin, Disciplina Endocrinol, Unidade Suprarrenal & Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol, Lab Invest Med, LIM 42, BR-05403900 Sao Paulo, SP - Brazil

^[2] Hosp Canc Barretos, Ro - Brazil

^[3] Univ Sao Paulo, Hosp Clin, Div Anat Patol, Lab Patol Hepat LIM14, Fac Med, BR-05403900 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Serv Endocrinol, Inst Canc Estado Sao Paulo, Fac Med, BR-05403900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Hormone and Metabolic Research; v. 47, n. 9, p. 656-661, AUG 2015.
• Web of Science Citations: 5

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 ((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. (AU)

• FAPESP's process: 11/09092-0 - Role of LIN28, a RNA-binding protein, in adrenocortical tumorigenesis
• Grantee: André Murad Faria
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/21272-6 - Analysis of DICER1 gene in pediatric and adult adrenocortical tumors
• Grantee: Madson Queiroz Almeida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 06/00244-3 - Study of IGF-II growth factor expression and SF-1 and DAX-1 transcription factors in adrenocortical tumors in children and adults
• Grantee: Madson Queiroz Almeida
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)