title: Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) and guanylate kinase 1 (GUK1) are differentially expressed in GH-secreting adenomas.
abstract: Pituitary tumors, adenomas in their vast majority, represent around 10-15% of the intracranial neoplasms. Pituitary carcinomas are exceedingly rare. Clinically, these neoplasms cause hormonal dysfunctions, and mass effect symptoms as headache and visual disorders in the case of macroadenomas. Pituitary tumorigenesis is still poorly understood. In order to investigate the expression of cancer-related genes in pituitary tumors, we employed a human cancer cDNA macroarray membrane with 1176 well-characterized human genes related to cancer and tumor biology. We were able to identify several differentially expressed genes, among them hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) and guanylate kinase 1 (GUK1) which were over expressed in a pool of clinically nonfunctioning pituitary adenomas, compared with a spinal cord metastasis of a nonfunctioning pituitary carcinoma. HGS and GUK1 mRNA expression were chosen to be validated by quantitative RT-qPCR, however, only GUK1 had the differential expression confirmed between the adenomas and the metastasis of a pituitary carcinoma. We have also investigated HGS and GUK1 mRNA expressions in a series of 46 pituitary adenomas (18 nonfunctioning, 12 GH-secreting, nine PRL-secreting, and seven ACTH-secreting adenomas). HGS and GUK1 were significantly over expressed in GH-secreting adenomas, compared with ACTH-secreting adenomas and nonfunctioning tumors, and with PRL-secreting adenomas, respectively. We have shown that these genes, involved in tumorigenesis in other tissues, are as well over expressed in the pituitary tumors, however, their role in the oncogenesis of these tumors need to be further investigated.
authors.affiliation: Laboratory for Cellular and Molecular Endocrinology-LIM/25, University of Sao Paulo Medical School, Sao Paulo-SP, Brazil.
authors.forename: Anderson Alves
authors.initials: AA
authors.lastname: da Rocha
authors.forename: Ricardo Rodrigues
authors.initials: RR
authors.lastname: Giorgi
authors.forename: Sandra Valeria
authors.initials: SV
authors.lastname: de Sa
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Correa-Giannella
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Fortes
authors.forename: Ana Mercedes
authors.initials: AM
authors.lastname: Cavaleiro
authors.forename: Marcio Carlos
authors.initials: MC
authors.lastname: Machado
authors.forename: Valter Angelo
authors.initials: VA
authors.lastname: Cescato
authors.forename: Marcello Delano
authors.initials: MD
authors.lastname: Bronstein
authors.forename: Daniel
authors.initials: D
authors.lastname: Giannella-Neto
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics / Q000378:metabolism*; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015175:Prolactinoma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; D012333:RNA, Messenger; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D051528:Guanylate Kinases