title: Proteins differentially expressed in human beta-cells-enriched pancreatic islet cultures and human insulinomas.
abstract: In view of the great demand for human beta-cells for physiological and medical studies, we generated cell lines derived from human insulinomas which secrete insulin, C-peptide and express neuroendocrine and islet markers. In this study, we set out to characterize their proteomes, comparing them to those of primary beta-cells using DIGE followed by MS. The results were validated by Western blotting. An average of 1800 spots was detected with less than 1% exhibiting differential abundance. Proteins more abundant in human islets, such as Caldesmon, are involved in the regulation of cell contractility, adhesion dependent signaling, and cytoskeletal organization. In contrast, almost all proteins more abundant in insulinoma cells, such as MAGE2, were first described here and could be related to cell survival and resistance to chemotherapy. Our proteomic data provides, for the first time, a molecular snapshot of the orchestrated changes in expression of proteins involved in key processes which could be correlated with the altered phenotype of human beta-cells. Collectively our observations prompt research towards the establishment of bioengineered human beta-cells providing a new and needed source of cultured human beta-cells for beta-cell research, along with the development of new therapeutic strategies for detection, characterization and treatment of insulinomas.
authors.affiliation: Instituto de Química, Departamento de Bioquímica, Universidade de São Paulo (USP), São Paulo, Brazil.
authors.forename: Letícia F
authors.initials: LF
authors.lastname: Terra
authors.forename: Priscila C
authors.initials: PC
authors.lastname: Teixeira
authors.forename: Rosangela A M
authors.initials: RA
authors.lastname: Wailemann
authors.forename: André
authors.initials: A
authors.lastname: Zelanis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmisano
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Martin R
authors.initials: MR
authors.lastname: Larsen
authors.forename: Leticia
authors.initials: L
authors.lastname: Labriola
authors.forename: Mari C
authors.initials: MC
authors.lastname: Sogayar
mesh_terms: D000328:Adult; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism*; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D008875:Middle Aged; D061251:Primary Cell Culture; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques; D014407:Tumor Cells, Cultured; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D058950:Melanoma-Specific Antigens; D020543:Proteome; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: CALD1; Caldesmon; Diabetes; Insulinomas; Islets; MAGE-A2; Mammalian biology; Mass spectrometry; Melanoma Associated Antigen-A2; NR6A1; Nuclear Receptor Subfamily 6 Group A Member 1; OTU domain-containing protein 7A; OTUD7A; Pancreatic cell biology