Article (Scientific journals)
Gs alpha overexpression and loss of Gs alpha imprinting in human somatotroph adenomas: association with tumor size and response to pharmacologic treatment.
Picard, Christophe; Silvy, Monique; Gerard, c et al.
2007In International Journal of Cancer, 121 (6), p. 1245-1252
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Keywords :
Adenoma/drug therapy/genetics/pathology; Antineoplastic Agents, Hormonal/therapeutic use; Blotting, Western; DNA Methylation; Drug Resistance, Neoplasm/genetics; GTP-Binding Protein alpha Subunits, Gs/genetics; Genomic Imprinting; Growth Hormone-Secreting Pituitary Adenoma/drug therapy/genetics/pathology; Humans; Octreotide/therapeutic use; Prolactinoma/drug therapy/genetics/pathology; RNA, Messenger/analysis; Reverse Transcriptase Polymerase Chain Reaction
Abstract :
[en] Gs alpha, the alpha-subunit of the heterotrimeric GTP-binding protein, is coded from the GNAS gene, which is imprinted in a tissue-specific manner. Gs alpha is paternally silenced in normal pituitary, but Gs alpha imprinting relaxation is found in some tumoral tissue. In addition, Gs alpha mRNA levels are high in some somatotroph adenomas not bearing the active Gs alpha mutant, the gsp oncogene. In this study, the impact of loss of imprinting on Gs alpha expression level and on tumoral phenotype has been investigated. We compared the expression and imprinting of 4 transcripts of GNAS locus (NESP55, XL alpha s, exon 1A, Gs alpha) of 60 somatotroph adenomas with those of 23 lactotroph adenomas. The paternal and maternal transcripts were quantified using allele-specific real-time PCR and FokI polymorphism. Moreover, the methylation of exon 1A DMR was analyzed. As is the case for the gsp oncogene, high Gs alpha expression in gsp- tumors was associated with smaller tumor size and better octreotide sensitivity. A strong imprinting relaxation (percentage of paternal Gs alpha expression >or=7.5%) was found only in gsp- tumors. The loss of Gs alpha imprinting was associated with a decrease in exon 1A mRNA expression. Unexpectedly, the methylation status of exon 1A DMR was not modified in relaxed tumors. Maternal Gs alpha mRNA level decreased with exon 1A level, and consequently the loss of Gs alpha imprinting did not induce the expected Gs alpha overexpression. Finally, XL alpha s mRNA level correlated with that of paternal Gs alpha and of NESP55 showing the complexity of gene regulation in the GNAS locus.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Picard, Christophe
Silvy, Monique
Gerard, c
Buffat, Christophe
Lavaque, Esteban
Figarella-Branger, Dominique
Dufour, Henri
Gabert, Jean
Beckers, Albert ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Brue, Thierry
Enjalbert, Alain
Barlier, Anne
Language :
English
Title :
Gs alpha overexpression and loss of Gs alpha imprinting in human somatotroph adenomas: association with tumor size and response to pharmacologic treatment.
Publication date :
15 September 2007
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
121
Issue :
6
Pages :
1245-1252
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 22 June 2010

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