Characterization of Prophet of Pit-1 gene expression in normal pituitary and pituitary adenomas in humans.
Prophet of Pit-1 (Prop-1), which is a paired-like homeodomain transcription factor, is capable of binding to sites in an early enhancer of the Pit-1 gene and regulating its expression. According to a previous report, Prop-1 messenger RNA (mRNA) is expressed in the developing pituitary gland before Pit-1 mRNA expression and maximum expression are observed at e 12.0. After e 14.5, Prop-1 mRNA expression rapidly decreases, and only trace amounts of mRNA are detectable in adult mouse pituitary. Human Pit-1 is expressed considerably, not only in normal adult pituitary but also in pituitary adenomas, so we studied human Prop-1 gene expression in adult pituitary and pituitary adenomas. We also cloned human Prop-1 complementary DNA (cDNA) and sequenced the Prop-1 cDNAs in pituitary adenomas. The amino acid sequence of human Prop-1 cDNA that we cloned was identical to that of the previously reported sequence, except Thr substituted at codon 142 instead of Ala. This amino acid substitution is considered to be a polymorphism because it did not alter transcriptional activity, and 7 of 28 alleles were Ala. Human Prop-1 transcript was detected in normal adult pituitary, by Northern blot analysis, and in all pituitary adenomas examined by RT-PCR analysis. The expression of human Prop-1 in pituitary adenomas was confirmed by in situ hybridization in one of the somatotroph adenomas. The sequence analysis of human Prop-1 cDNAs in these pituitary adenomas revealed that there were no mutations, except 5 silent nucleic acid substitutions, suggesting that mutations of Prop-1 gene do not represent a frequent mechanism of human pituitary tumorigenesis.
Nakamura
Y
Y
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Usui
T
T
Mizuta
H
H
Murabe
H
H
Muro
S
S
Suda
M
M
Tanaka
K
K
Tanaka
I
I
Shimatsu
A
A
Nakao
K
K
D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D001483:Base Sequence; D003001:Cloning, Molecular; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D014158:Transcription, Genetic
D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D012333:RNA, Messenger