The expression of the antiproliferative gene ZAC is lost or highly reduced in nonfunctioning pituitary adenomas.
The ZAC gene encodes a new zinc-finger protein that concomitantly induces apoptosis and cell cycle arrest and localizes to chromosome 6q24-q25, a well-known hot spot related to cancer. ZAC is highly expressed in the anterior pituitary gland, and its ablation by antisense targeting promotes pituitary cell proliferation. Here we investigate ZAC status in pituitary tumors to evaluate its role in pituitary tumorigenesis. Interest ingly, a strong reduction or absence of ZAC mRNA and protein expres sion was detected in nonfunctioning pituitary adenomas, whereas in clin ically active pituitary neoplasias, the decrease in ZAC expression was variable. Loss of expression was not associated with a mutation of the ZAC gene. Our observations suggest that alternative mechanisms of gene inactivation and/or altered regulation of the ZAC gene occur in nonfunctioning pituitary adenomas.
Pagotto
U
U
Max Planck Institute of Psychiatry, Munich, Germany.
Arzberger
T
T
Theodoropoulou
M
M
Grübler
Y
Y
Pantaloni
C
C
Saeger
W
W
Losa
M
M
Journot
L
L
Stalla
G K
GK
Spengler
D
D
D000236:Adenoma / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002455:Cell Division; D018076:DNA, Complementary / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D016335:Zinc Fingers
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; C106464:PLAGL1 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors