title: Histological features and expression of enzymes implicated in melatonin synthesis in pineal parenchymal tumours and in cultured tumoural pineal cells.
abstract: Pineal parenchymal tumours (PPT) are rare neoplasms and there have been few in vitro studies. Their capacity for synthesizing and secreting melatonin has been only partially examined. We investigated the presence of messenger RNA (mRNA) encoding tryptophan hydroxylase (TPH), arylalkylamine N-acetyltransferase (AANAT), hydroxyindol-O-methyltransferase (HIOMT), three enzymes involved in melatonin synthesis, and c-myc, a tumoural marker, in 10 PPT, one papillary tumour of the pineal region (PTPR), cell cultures derived from four PPTs and from three other tumours of the pineal region, and in normal pineal gland. Moreover, protein expression of TPH was investigated in three PPT and PTPR. Quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry were used and the melatonin production by tumoural cells in vitro was analysed by radioimmunoassay. We showed that all the tumoural tissues and cells contained c-myc mRNA. mRNAs encoding TPH, AANAT and HIOMT were detected in all PPT, suggesting that tumour cells can synthesize melatonin. Only PPT expressed TPH protein. Cultured cells lost expression of transcripts throughout passages even if ultrastructural study revealed the presence of characteristic organelles in these tumoural cells. Nevertheless, the basal secretion of melatonin observed in one PPT culture is in favour of a maintained melatonin production and secretion by tumoural pinealocytes, but melatonin production was not stimulated by a beta noradrenergic agonist. Moreover, PTPR never expressed mRNA encoding TPH, AANAT and HIOMT. Our results may contribute to a better understanding of the biology of PTT and PTPR and may help to the diagnosis of these rare tumours.
authors.affiliation: INSERM, U842, Université de Lyon, Faculté de Médecine Laennec, UMR-S842, Lyon, France. montange@lyon.inserm.fr
authors.forename: M
authors.initials: M
authors.lastname: Fevre-Montange
authors.forename: J
authors.initials: J
authors.lastname: Champier
authors.forename: A
authors.initials: A
authors.lastname: Szathmari
authors.forename: C
authors.initials: C
authors.lastname: Brisson
authors.forename: A
authors.initials: A
authors.lastname: Reboul
authors.forename: C
authors.initials: C
authors.lastname: Mottolese
authors.forename: F
authors.initials: F
authors.lastname: Fauchon
authors.forename: B
authors.initials: B
authors.lastname: Claustrat
authors.forename: A
authors.initials: A
authors.lastname: Jouvet
mesh_terms: D000121:Acetylserotonin O-Methyltransferase / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D047068:Arylalkylamine N-Acetyltransferase / Q000096:biosynthesis; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008550:Melatonin / Q000096:biosynthesis; D008875:Middle Aged; D010870:Pineal Gland / Q000201:enzymology* / Q000473:pathology*; D010871:Pinealoma / Q000201:enzymology* / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014365:Tryptophan Hydroxylase; D000121:Acetylserotonin O-Methyltransferase; C478879:AANAT protein, human; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin