title: Metallothionein isoform 3 gene is differentially expressed in corticotropin-producing pituitary adenomas.
abstract: In order to search for candidate genes related to pituitary adenoma aggressiveness, the present investigation was intended to compare the mRNA expression profile from a pool of four nonfunctional pituitary adenomas (NFPA) with a spinal cord metastasis of a nonfunctional pituitary carcinoma (MNFPC). The metallothionein isoform 3 (MT3) gene was differentially expressed in nonfunctional adenomas in comparison to the metastasis of nonfunctional carcinoma. A microarray dataset comprising 19,881 probes was employed for comparing expression profiles of a spinal cord metastasis of a nonfunctional pituitary carcinoma with a pool of four nonfunctional pituitary adenomas. RT-qPCR confirmed the microarray findings and was used to investigate MT3 mRNA gene expression in tumor samples of a series of 52 different pituitary adenoma subtypes comprising 10 corticotropin (ACTH)-producing, 18 growth hormone (GH)-producing, 8 prolactin (PRL)-producing, and 16 nonfunctional adenomas. Microarray data analysis by GeneSifter program unveiled Gene Ontology terms related to zinc ion-binding activity closely related to MT3 function. MT3 mRNA expression was statistically significantly higher in ACTH-producing pituitary adenomas and in nonfunctional pituitary adenomas in comparison to the other pituitary adenoma subtypes. The more abundant expression of this gene in ACTH-producing pituitary adenomas suggests that MT3 could be related to distinct pituitary cell lineage regulating the activity of some transcription factor of importance in hormone production and/or secretion.
authors.affiliation: Laboratory for Cellular and Molecular Endocrinology - LIM25, São Paulo, Brazil.
authors.forename: R R
authors.initials: RR
authors.lastname: Giorgi
authors.forename: M L C
authors.initials: ML
authors.lastname: Correa-Giannella
authors.forename: A P M
authors.initials: AP
authors.lastname: Casarini
authors.forename: M C
authors.initials: MC
authors.lastname: Machado
authors.forename: M D
authors.initials: MD
authors.lastname: Bronstein
authors.forename: V A
authors.initials: VA
authors.lastname: Cescato
authors.forename: D
authors.initials: D
authors.lastname: Giannella-Neto
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D015870:Gene Expression; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000556:secondary; D011388:Prolactin / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013120:Spinal Cord Neoplasms / Q000556:secondary
chemical_list: D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin