RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumours in the ectopic-ACTH syndrome.
OBJECTIVE
ACTH is frequently produced in non-pituitary tumours, leading to the ectopic-ACTH syndrome, but the molecular mechanisms of its expression remain obscure. This study was aimed at understanding the transcription mechanisms of the ACTH-precursor gene in carcinoid tumours of the lung or thymus.


METHODS
Transcripts coding for a series of corticotroph-associated transcription factor genes were detected, together with markers of the corticotroph phenotype. We studied a series of 41 carcinoid tumours including 15 with proven ectopic-ACTH syndrome.


METHODS
Specific RT-PCR reactions were designed for each gene including alternatively spliced isoforms.


RESULTS
The markers of the corticotroph phenotype were detected in all ACTH-positive tumours. Expression of the Tpit and Pitx1 genes were not restricted to ACTH-positive tumours but were also detected in many ACTH-negative carcinoids. Only a subset of ACTH-negative tumours expressed NAK-1/Nur77, and NeuroD1 expression was detected in approximately 50% of the tumours regardless of their secretory status. The glucocorticoid receptor alpha was detected in every tumour in contrast to its beta isoform detectable in a few tumours only. Chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) and peroxisome proliferator-activated receptor (PPAR) gamma2 were expressed in 50% of the tumours of each group whereas PPARgamma1 was expressed in almost every tumour.


CONCLUSIONS
ACTH-positive carcinoids do not share a characteristic expression pattern of the corticotroph-associated transcription factor genes, suggesting that the transcriptional mechanisms of the ACTH-precursor gene differ from those in normal pituitary corticotrophs. Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation.
Messager
M
M
Institut Cochin, INSERM U567-CNRS UMR8107, 24 rue du faubourg Saint Jacques, 75014, Paris, France.
Carrière
C
C
Bertagna
X
X
de Keyzer
Y
Y
D000182:ACTH Syndrome, Ectopic / Q000378:metabolism*; D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001984:Bronchial Neoplasms / Q000235:genetics / Q000378:metabolism*; D051838:COUP Transcription Factor I / Q000235:genetics; D002276:Carcinoid Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D051838:COUP Transcription Factor I; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D011965:Receptors, Glucocorticoid; D020825:T-Box Domain Proteins; D014157:Transcription Factors; C497589:NR2F1 protein, human; C486589:TBX19 protein, human; C411470:glucocorticoid receptor alpha; C101485:homeobox protein PITX1; C093564:Neurogenic differentiation factor 1