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

Imagem de Miniatura
Arquivos
art_SOUSA_DAX1_Overexpression_in_Pediatric_Adrenocortical_Tumors_A_Synergic_2015.PDF (560.77 KB)
Citações na Scopus
9
Tipo de produção
article
Data de publicação
2015
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
GEORG THIEME VERLAG KG
Autores
SOARES, I. C.
DOMINGUES, V. B.
Citação
HORMONE AND METABOLIC RESEARCH, v.47, n.9, p.656-661, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
DAX1, SF1, expression, adrenocortical tumors
URI
https://observatorio.fm.usp.br/handle/OPI/11832
Referências
  1. Achermann JC, 1999, NAT GENET, V22, P125
  2. Almeida MQ, 2007, HORM METAB RES, V39, P461, DOI 10.1055/s-2007-981476
  3. Almeida MQ, 2008, J CLIN ENDOCR METAB, V93, P3524, DOI 10.1210/jc.2008-0065
  4. Almeida MQ, 2010, J CLIN ENDOCR METAB, V95, P1458, DOI 10.1210/jc.2009-2040
  5. Bassett MH, 2005, J CLIN ENDOCR METAB, V90, P5446, DOI 10.1210/jc.2005-0836
  6. BURRIS TP, 1995, BIOCHEM BIOPH RES CO, V214, P576, DOI 10.1006/bbrc.1995.2324
  7. Conde I, 2004, BREAST CANCER RES, V6, pR140, DOI 10.1186/bcr766
  8. Faria AM, 2012, MOL CELL ENDOCRINOL, V351, P52, DOI 10.1016/j.mce.2011.09.040
  9. Fassnacht M, 2009, CANCER, V115, P243, DOI 10.1002/cncr.24030
  10. Figueiredo BC, 2005, J CLIN ENDOCR METAB, V90, P615, DOI 10.1210/jc.2004-0942
  11. Garcia-Aragoncillo E, 2008, ONCOGENE, V27, P6034, DOI 10.1038/onc.2008.203
  12. Giordano TJ, 2009, CLIN CANCER RES, V15, P668, DOI 10.1158/1078-0432.CCR-08-1067
  13. Glover CH, 2006, PLOS COMPUT BIOL, V2, P1463, DOI 10.1371/journal.pcbi.0020158
  14. Helguero LA, 2006, ENDOCRINOLOGY, V147, P3249, DOI 10.1210/en.2005-1651
  15. Khalfallah O, 2009, STEM CELLS, V27, P1529, DOI 10.1002/stem.78
  16. Kinsey M, 2009, CANCER RES, V69, P9047, DOI 10.1158/0008-5472.CAN-09-1540
  17. Lalli E, EXPERT OPIN THER TAR, V14, P169
  18. Lalli E, 1998, ENDOCRINOLOGY, V139, P4237, DOI 10.1210/en.139.10.4237
  19. Lalli E, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2013.446
  20. Latronico AC, 1997, J CLIN ENDOCR METAB, V82, P1317, DOI 10.1210/jc.82.5.1317
  21. Mizusaki H, 2003, MOL ENDOCRINOL, V17, P507, DOI 10.1210/me.2002-0362
  22. MUSCATELLI F, 1994, NATURE, V372, P672, DOI 10.1038/372672a0
  23. Niakan KK, 2006, MOL GENET METAB, V88, P261, DOI 10.1016/j.ymgme.2005.12.010
  24. Oda T, 2009, AM J PATHOL, V175, P1235, DOI 10.2353/ajpath.2009.090010
  25. Olaussen KA, 2006, NEW ENGL J MED, V355, P983, DOI 10.1056/NEJMoa060570
  26. Park SY, 2005, DEVELOPMENT, V132, P2415, DOI 10.1242/dev.01826
  27. Reincke M, 1998, J CLIN ENDOCR METAB, V83, P2597, DOI 10.1210/jc.83.7.2597
  28. Sbiera S, 2010, J CLIN ENDOCR METAB, V95, pE161, DOI 10.1210/jc.2010-0653
  29. Shibata H, 2001, MOL GENET METAB, V74, P206, DOI 10.1006/mgme.2001.3231
  30. Tissier F, 2005, CANCER RES, V65, P7622, DOI 10.1158/0008-5472.CAN-05-0593
  31. Vilain E, 1997, BIOCHEM MOL MED, V61, P1, DOI 10.1006/bmme.1997.2601
  32. Wieneke JA, 2003, AM J SURG PATHOL, V27, P867, DOI 10.1097/00000478-200307000-00001
  33. ZANARIA E, 1994, NATURE, V372, P635, DOI 10.1038/372635a0

Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - LIM/42
Carregar mais